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Abstract
The development of autologous fat grafting to augment or reconstruct tissue defects has become an increasingly popular modality among plastic surgeons. Despite its popularity, a standardized fat grafting protocol has yet to be developed. Great variations exist with regard to almost all the technical features, yielding a reported fat graft survivability that ranges from 40% to 80%. Recent bench approaches have been proposed to improve the long-term viability of fat grafts: although promising results have been shown, empirical evidence has yet to prove the superiority of one particular method. Nevertheless, currently available literature still provides some evidence for optimal results in differing clinical scenarios, in the wait of validating and ultimate studies.The issues of enriched fat grafting techniques and variations in harvesting and delivery in the background of US regulatory constraints demand alterations and variations in techniques. These only complicate the process of validation of any single technique. However, recent studies have brought us closer to making informed decisions on technical choices in lipotransfer. These are elaborated on in this review.
... 16,17 Harvested adipose tissue is composed of mature adipocytes, extracellular matrix, and a stromal vascular fraction (SVF) that is constituted by several types of cells including adiposederived stem cells (ADSCs). 18,19 Although remains an area of debate, ADSC-enriched grafts have been associated with better graft viability and outcome after transplantation. [19][20][21] Furthermore, different harvesting techniques can result in different outcomes in regards to fat graft take. ...
... 18,19 Although remains an area of debate, ADSC-enriched grafts have been associated with better graft viability and outcome after transplantation. [19][20][21] Furthermore, different harvesting techniques can result in different outcomes in regards to fat graft take. 16 Therefore, establishing best-practice guidelines for fat grafting methodology is of utmost importance moving forward to minimize fat graft loss. ...
Autologous fat transplantation has become increasingly popular in recent years. Its biocompatable properties and availability made it a widely used treatment modality for soft tissue augmentation and volume replacement in both reconstructive and aesthetic plastic surgery. Multiple protocols and clinical applications have been described in the literature, with wide variations in the harvesting, processing, and injection techniques. In this review, the authors will discuss the basic principles and clinical applications of fat grafting in plastic and reconstructive surgery. The article will then conclude with a discussion of fat grafting limitations as well as potential future applications, giving the reader a well-rounded understanding of autologous fat transfer.
... SVF as a regenerative modality (Table 1) Fat grafting The increasing use of autologous lipotransfer, or fat grafting, in plastic and reconstructive surgery has warranted an exploration of novel ways to improve clinical outcomes. 12,13 As it currently stands, clinicians are challenged by significant variability in fat graft retention. Reported resorption rates range from 25 to 80%. 14 Much of the volume loss is attributed to the tendency of mature adipocytes to undergo cell death after injection into the recipient site. ...
... 29 Consequently, SVF is subject to a separate set of regulations under Section 351 of the Public Health System Act for biological products. 12,30,31 Furthermore, in consideration of the time practicalities in plastic and reconstructive procedures, the time allotted to collagenase digestion poses yet another inconvenience. ...
Stromal Vascular Fraction (SVF) is a heterogeneous collection of cells contained within adipose tissue that is traditionally isolated using enzymes such as collagenase. With the removal of adipose cells, connective tissue and blood from lipoaspirate, comes the SVF, a mix including mesenchymal stem cells, endothelial precursor cells, T regulatory cells, macrophages, smooth muscle cells, pericytes and preadipocytes. In part 1 of our 2-part series, we review the literature with regards to the intensifying interest that has shifted toward this mixture of cells, particularly due to its component synergy and translational potential. Trials assessing the regenerative potential of cultured Adipose Derived Stem Cells (ADSCs) and SVF demonstrate that SVF is comparably effective in treating conditions ranging from radiation injuries, burn wounds and diabetes, amongst others. Aside from their use in chronic conditions, SVF enrichment of fat grafts has proven a major advance in maintaining fat graft volume and viability. Many SVF studies are currently in preclinical phases or are moving to human trials. Overall, regenerative cell therapy based on SVF is at an early investigative stage but its potential for clinical application is enormous.
... 7,11,12 SVF and matrix are composed of various cells, including ADSCs, vascular smooth muscle cells, MSCs, pericytes, fibroblasts, endothelial cells, hematopoietic cells, and other immune cells. [13][14][15][16][17] Treatment with SVF is one of the most recent novel methods in the field of regenerative medicine, with promising results in the majority of patients. [18][19][20][21] There are two general ways to obtain SVF: the first method is a chemical protocol that involves enzymatic digestion, and the second method is a physical protocol that involves mechanical separation from connective tissue. ...
Backgrounds and Objective
During fat transplantation, adipose tissue is removed from the body and injected into different areas under the skin. The goal of this review article is to look into the efficacy and applicability of fat transplantation in regenerative medicine and rejuvenation, including Nanofat, Microfat, and Millifat.
Methods
As a search strategy and study selection, we searched the PubMed and Medline databases until 2023 using related keywords (e.g., Nanofat, Microfat and Millifat, Regenerative Medicine, and Rejuvenation).
Results
Autologous fat transplantation has no risk of an allergic reaction or rejection of the transplant by the individual. Autologous adipose tissue is considered an ideal filler for facial rejuvenation and is suggested as the most biocompatible and non‐immunogenic skin filler. Adipose tissue transplant may have semi‐permanent to permanent effects. According to recent reports, adipose tissues possess a high percentage of mature stem cells. The effect of regenerating adipose tissue and its intrinsic cells can be described as an obvious process. Variations in the sizes of adipose tissues can result in different results depending on the surgical site. Based on topographic assessment, graft fats are assigned depending on the anatomical locations and the size such as Millifat (2–2.5 mm), Microfat (1 mm), and Nanofat (500 μm or less).
Conclusion
Some characteristics of fat tissue increase its effectiveness, such as increasing stem cells, growth factors, cytokines, and compounds effective in repair, regeneration, and rejuvenation.
... Subsequently, purified stem cell therapy is highly regulated by the FDA and its application is prohibited except for specific conditions such as hematopoiesis after chemotherapy [22]. Because of a shift toward SVF application in US private clinics, the FDA explicitly declared that the enzymatic disruption or ultrasonic cavitation of fat tissue for obtaining SVF is considered as 'more than minimal manipulation', which makes it unapproved for human use [22,117]. It is worth mentioning that different countries have different regulatory standpoints. ...
Despite recent advances in microsurgical techniques, functional recovery following peripheral nerve injury remains slow and inadequate. Poor peripheral nerve regeneration not only leaves patients with significant impairments, but also commonly leads to the development of debilitating neuropathic pain. Recent research has demonstrated the potential therapeutic benefits of adipose-derived stem cells, to enhance nerve regeneration. However, clinical translation remains limited due to the current regulatory burdens of the US FDA. A reliable and immediately translatable alternative is autologous fat grafting, where native adipose-derived stem cells present in the transferred tissue can potentially act upon regenerating axons. This review presents the scope of adipose tissue-based therapies to enhance outcomes following peripheral nerve injury, specifically focusing on their role in regeneration and ameliorating neuropathic pain.
... Autologous fat is currently employed for a variety of cosmetic or reconstructive indications including sequelae of radiation therapy, breast augmentation, trauma, facial rejuvenation, and orbital fracture [1,2]. Despite the advantages of the wide sources of fat and its nonimmunogenic properties, the long-term poor outcomes of fat grafting caused by high absorption rate are critical drawbacks and a major limitation [3,4]. As reported, the survival rate of grafted fat ranges from 20 to 80% [5,6]. ...
Background
Fat grafting, as a standard treatment for numerous soft tissue defects, remains unpredictable and technique-dependent. Human adipose-derived stem cells (hADSCs) are promising candidates for cell-assisted therapy to improve graft survival. As free-living fat requires nutritional and respiratory sources to thrive, insufficient and unstable vascularization still impedes hADSC-assisted therapy. Recently, cytotherapy combined with modified mRNA (modRNA) encoding vascular endothelial growth factor (VEGF) has been applied for the treatment of ischemia-related diseases. Herein, we hypothesized that VEGF modRNA (modVEGF)-engineered hADSCs could robustly enhance fat survival in a fat graft transplantation model.
Methods
hADSCs were acquired from lipoaspiration and transfected with modRNAs. Transfection efficiency and expression kinetics of modRNAs in hADSCs were first evaluated in vitro. Next, we applied an in vivo Matrigel plug assay to assess the viability and angiogenic potential of modVEGF-engineered hADSCs at 1 week post-implantation. Finally, modVEGF-engineered hADSCs were co-transplanted with human fat in a murine model to analyze the survival rate, re-vascularization, proliferation, fibrosis, apoptosis, and necrosis of fat grafts over long-term follow-up.
Results
Transfections of modVEGF in hADSCs were highly tolerable as the modVEGF-engineered hADSCs facilitated burst-like protein production of VEGF in both our in vitro and in vivo models. modVEGF-engineered hADSCs induced increased levels of cellular proliferation and proangiogenesis when compared to untreated hADSCs in both ex vivo and in vivo assays. In a fat graft transplantation model, we provided evidence that modVEGF-engineered hADSCs promote the optimal potency to preserve adipocytes, especially in the long-term post-transplantation phase. Detailed histological analysis of fat grafts harvested at 15, 30, and 90 days following in vivo grafting suggested the release of VEGF protein from modVEGF-engineered hADSCs significantly improved neo-angiogenesis, vascular maturity, and cell proliferation. The modVEGF-engineered hADSCs also significantly mitigated the presence of fibrosis, apoptosis, and necrosis of grafts when compared to the control groups. Moreover, modVEGF-engineered hADSCs promoted graft survival and cell differentiation abilities, which also induced an increase in vessel formation and the number of surviving adipocytes after transplantation.
Conclusion
This current study demonstrates the employment of modVEGF-engineered hADSCs as an advanced alternative to the clinical treatment involving soft-tissue reconstruction and rejuvenation.
The heterogeneous population of cells obtained from processed adipose tissue, known as stromal vascular fraction (SVF), exhibits immunomodulatory and angiogenic properties. The therapeutic efficacy of SVF has been substantiated in numerous diseases, instilling hope for its clinical application as a cellular therapy. This study aims to provide a comprehensive analysis of the scholarly literature on SVF, including its worldwide progression, highlighting significant literatures, temporal development, research clusters, current active topics, and emerging trends. The combination of CiteSpace, HistCite Pro, and VOS Viewer tools was used to analyze the SVF literature. The overall panorama of the field is elucidated in terms of publication count, timeline, institutional distribution, journal coverage, and authors' contributions. In addition, this analysis explores the literature and keywords through the lens of co-occurrence, citation, and co-citation frequencies. Clustering algorithms are employed to track the trajectory of the literature further, providing insight into its development. The findings offer a comprehensive overview of the progress made in the SVF field, highlighting distinct phases of development: the "Seedling period" from 1980 to 2010, the "Panicle period" from 2011 to 2016, and the "Flowering period" from 2017 to 2023. Within these periods, the evolution of ten clusters is unraveled, encompassing topics such as vascular disease, CD34 expression, adipose tissue macrophage in 2013, cell-assisted lipotransfer, and knee osteoarthritis. In summary, this bibliometric study, conducting a quantitative analysis of publications in SVF research, encompasses a global overview of research, an analysis of pivotal literature in the field, research hotspots, and emerging frontiers.
Background:. Fat is an active and dynamic tissue composed of adipocytes supported by a structural framework known as the stromal vascular fraction (SVF). SVF is traditionally isolated by enzymatic processing, but new methods are being investigated to isolate it mechanically. Recent studies propose that fat harvested with larger cannulas has a higher survival rate, most likely due to a higher concentration of SVF.
Methods:. Lipoaspirates were obtained from 10 patients who underwent elective liposuction using a 5-mm and a 1-mm cannula attached to a syringe using standard pressure. The fat was aspirated from the same area at adjacent sites. An estimated 5-mm fat particles were also cut down to 1-mm using a micronizer (Marina Medical). A 5-cm3 volume of each sample was compressed through a 0.5-mm opening strainer and rinsed with normal saline to extrude the oil. The resultant SVF left on the strainer was then measured in a 1-cm3 syringe.
Results:. The volume extracted from a 5-mm cannula (mean, 0.23 cm3; SD, 0.10) versus a 1-mm cannula (mean, 0.11 cm3; SD, 0.06) was statistically significant (P = 0.009). An H&E-stained slide from the SVF was obtained for confirmation. Finally, 5-mm fat particles cut down to 1-mm particles using the micronizer resulted in an average volume of 0.20 cm3, which was higher than the average volume harvested with a 1-mm cannula.
Conclusions:. Harvesting with a 5-mm cannula resulted in significantly more SVF than harvesting with a 1-mm cannula. Resizing fat particles harvested with a larger cannula down to 1-mm resulted in higher SVF than SVF obtained with a 1-mm cannula directly.
Autologous fat grafting is widely used for soft-tissue augmentation and replacement in reconstructive and aesthetic surgery providing a biocompatible, natural and inexpensive method. Multiple approaches have been developed in the past years, varying in the location of adipose tissue donor-sites, use of wetting solutions, harvesting, processing and placing techniques. Despite many advances in this subject, the lack of standardization in the protocols and the unpredictability of the resorption of the grafted tissue pose a significant limitation for graft retention and subsequent filling. In this review, we discuss several approaches and methods described over the last years concerning the harvesting of autologous fat grafts. We focus on contents such as the best donor-site, differences between existing harvesting techniques (namely tissue resection, hand aspiration or liposuction techniques), recommended harvesting cannula diameters, pressure application and volume of wetting solution injected prior aspiration. Results and comparisons between methods tend to vary according to the outcome measured, thus posing a limitation to pinpoint the most efficient methods to apply in fat grafting. Additionally, the lack of a standard assay to determine viability or volume augmentation of fat grafting remains another limitation to obtain universally accepted grafting procedures and protocols.
Importance
Autologous fat grafting has revolutionized the field of facial soft-tissue augmentation, despite a lack of standardization. Objective data are needed to arrive at consensus regarding the best technique for optimal volume retention.
Objective
To compare 3 fat-processing techniques with 3-dimensional (3-D) technology to explore the optimal fat-processing technique for improving the volume retention of grafted fat.
Design, Setting, and Participants
From September 2015 to December 2016, patients with facial asymmetry were treated by initial facial fat grafting at the Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Sixty-three patients (21 per group) were randomized to 1 of 3 fat-processing techniques: sedimentation, centrifugation, and cotton pad filtration. Patients underwent 3-D scanning preoperatively and at 1, 3, 6, and 12 months postoperatively. Patients who did not complete preoperative or postoperative follow-up and 3-D imaging were excluded from the analysis.
Intervention
Autologous fat grafting to correct facial asymmetry.
Main Outcomes and Measures
The percentage volume maintenance of each fat-processing technique was measured with 3-D software and analyzed with variance analysis.
Results
Of the 63 randomized patients, 30 (7 men, 23 women; mean [SD] age at surgery, 22.2 [8.0] years) completed follow-up. The mean (SD) percentage volume maintenance of the 3 groups at 1, 3, 6, and 12 months postoperatively was, respectively, 49% (4%), 45% (3%), 43% (3%), and 41% (3%) for the cotton pad filtration group; 41% (3%), 38% (4%), 36% (4%), and 34% (3%) for the centrifugation group; and 37% (4%), 34% (4%), 31% (3%), and 31% (3%) for sedimentation group. The variance analysis showed that the cotton pad filtration group demonstrated a statistically significant higher percentage volume maintenance in comparison with the centrifugation and sedimentation groups.
Conclusions and Relevance
The use of 3-D technology provides an objective and accurate way to evaluate different fat-processing techniques. Autologous fat processed by cotton pad filtration had a significant higher volume retention than did that processed by centrifugation and sedimentation technique.
Trial Registration
chictr.org.cn Identifier: ChiCTR-IOR-14005599
Level of Evidence
1.
Adipose/fat tissue provides an abundant source of stromal vascular fraction (SVF) cells for immediate administration and can also give rise to a substantial number of cultured, multipotent adipose-derived stromal cells (ADSCs). Recently, both SVF and ADSCs have gained wide-ranging translational significance in regenerative medicine. Initially used for cosmetic breast enhancement, this mode of treatment has found use in many diseases involving immune disorders, tissue degeneration, and ischaemic conditions. In this review, we try to address several important aspects of this field, outlining the biology, technology, translation, and challenges related to SVF- and ADSC-based therapies. Starting from the basics of SVF and ADSC isolation, we touch upon recently developed technologies, addressing elements of novel methods and devices under development for point-of-care isolation of SVF. Characterisation of SVF cells and ADSCs is also an evolving area and we look into unusual expression of CD34 antigen as an interesting marker for such purposes. Based on reports involving different cells of the SVF, we draw a potential mode of action, focussing on angiogenesis since it involves multiple cells, unlike immunomodulation which is governed predominantly by ADSCs. We have looked into the latest research, experimental therapies, and clinical trials which are utilising SVF/ADSCs in conditions such as multiple sclerosis, Crohn’s disease, peripheral neuropathy, osteoarthritis, diabetic foot ulcer, and so forth. However, problems have arisen with regards to the lack of proper regulatory guidelines for such therapies and, since the introduction of US Food and Drug Administration draft guidelines and the Reliable and Effective Growth for Regenerative Health Options that Improve Wellness (REGROW) Act, the debate became more public with regards to safe and efficacious use of these cells.
Optimization of fat grafting continues to gain increasing attention in the field of regenerative medicine. “Nanofat grafting” implements mechanical emulsification and injection of standard lipoaspirate for the correction of superficial rhytides and skin discoloration; however, little is known about the cellular constituents of the graft. Based on recent evidence that various stressors can induce progenitor activity, the authors hypothesized that the shear forces used in common fat grafting techniques may impact their regenerative capacities.
Lipoaspirates were obtained from 10 patients undergoing elective procedures. Half of each sample was subjected to nanofat processing; the other half was left unchallenged. The viscosity of each sample was measured for computational analysis. The stromal vascular fraction of each sample was isolated, quantified, and analyzed by means of flow cytometry with two multicolor fluorescence antibody panels.
Standard lipoaspirate is ideally suited for mechanical stress induction. The mechanical emulsification involved in nanofat processing did not affect cell number; however, viability was greatly reduced when compared with the stromal vascular fraction of standard lipoaspirate. Interestingly, nanofat processing resulted in stress-induced stromal vascular fraction with a higher proportion of endothelial progenitor cells, mesenchymal stem cells, and multilineage differentiating stress-enduring cells. Single-parameter analysis also revealed significant increases in CD34, CD13, CD73, and CD146 of the stress-induced stromal vascular fraction, markers associated with mesenchymal stem cell activity.
Mechanical processing used in techniques such as nanofat grafting induces the up-regulation of progenitor phenotypes consistent with multipotency and pluripotency. These data provide a first step in characterizing the potential regenerative benefits realized through stress induction in fat grafting.
Therapeutic, V.
The development of an engineered adipose tissue substitute capable of supporting reliable, predictable, and complete fat tissue regeneration would be of value in plastic and reconstructive surgery. For adipogenesis, a tissue engineering chamber (TEC) provides an optimized microenvironment that is both efficacious and reproducible; however, for reasons that remain unclear, tissues regenerated in a TEC consist mostly of connective rather than adipose tissue. Here we describe a chamber-based system for improving the yield of mature adipose tissue and discuss the potential mechanism of adipogenesis in tissue-chamber models. Adipose tissue flaps with independent vascular pedicles placed in chambers were implanted into rabbits. Adipose volume increased significantly during the observation period (week 1, 2, 3, 4, 16). Histomorphometry revealed mature adipose tissue with signs of adipose tissue remolding. The induced engineered constructs showed high-level expression of adipogenic (peroxisome proliferator-activated receptor γ), chemotactic (stromal cell-derived factor 1a), and inflammatory (interleukin 1 and 6) genes. In our system, the extracellular matrix may have served as a scaffold for cell migration and proliferation, allowing mature adipose tissue to be obtained in a chamber microenvironment without the need for an exogenous scaffold. Our results provide new insights into key elements involved in the early development of adipose tissue regeneration. This article is protected by copyright. All rights reserved.
© 2015 by the Wound Healing Society.
Although lipotransfer, or fat grafting, is a commonly used procedure in aesthetic and reconstructive surgery, there is still variability in graft survival and neoadipogenesis from one procedure to the next. A better understanding of the sequential molecular events occurring with grafting would allow us to strategize methods to improve the regenerative potency of the grafted tissue. These steps begin with an autophagic process, followed by the inclusion of stromal vascular fraction and matrix components. By tailoring and modifying each of these steps for a particular type of aesthetic or reconstructive procedure, strategic sequencing represents a dynamic approach to lipotransfer with the aim of maximizing adipocyte viability and growth. In the implementation of the strategic sequence, it remains important to consider the clinical viability of each step and its compliance with the US Food and Drug Administration regulations. This review highlights the basic science behind clinically translatable approaches to supplementing various fat grafting procedures.
In order to regenerate organs and functions has become known to the stem cells. Adult stem cells have the advantage that can be obtained from adult individuals without the ethical problems that brings the use of embryonic cells. Obtaining stem cells from adipose tissue (ASCs) has been a revolution because these cells can be obtained in large quantities with minimal discomfort and even with local anesthesia. Comparing the ASCs versus stem cells derived from bone marrow (BM-MSCs) their phenotypic characteristics and potential for differentiation are very similar. In this review we focus on the technique for obtaining ASCs, its molecular characteristics, their capacity for differentiation in mesodermal and no-mesodermal lineages, the most relevant preclinical and clinical trials executed at this time, as well as prospects for future use.
The use of autologous fat grafting is ideal in breast reconstruction. However, published data on long-term outcomes and instrumental results of fat grafting to the breast are lacking. The purpose of this study was to review the authors' experience of fat grafting, evaluating the effects related to the use of enhanced stromal vascular fraction (e-SVF) and fat grafting with platelet-rich plasma (PRP) in the maintenance of fat volume in breast reconstruction, comparing the results with a control group. Twenty-three patients aged 19-60 years affected by breast soft tissue defects were analyzed at the Plastic and Reconstructive Department of the University of Rome Tor Vergata. Ten patients were treated with SVF-enhanced autologous fat grafts, and 13 patients were treated with fat grafting + platelet-rich plasma. The patients in the control group (n = 10) were treated with centrifuged fat grafting injection according to Coleman's procedure. The patients treated with SVF-enhanced autologous fat grafts showed a 63% maintenance of the contour restoring and of three-dimensional volume after 1 year compared with the patients of the control group treated with centrifuged fat graft, who showed a 39% maintenance. In those patients who were treated with fat grafting and PRP, we observed a 69% maintenance of contour restoring and of three-dimensional volume after 1 year. As reported, the use of either e-SVF or PRP mixed with fat grafting produced an improvement in maintenance of breast volume in patients affected by breast soft tissue defect.
Adipose tissue is an abundant, accessible, and replenishable source of adult stem cells that can be isolated from liposuction waste tissue by collagenase digestion and differential centrifugation. These adipose-derived adult stem (ADAS) cells are multipotent, differentiating along the adipocyte, chondrocyte, myocyte, neuronal, and osteoblast lineages, and can serve in other capacities, such as providing hematopoietic support and gene transfer. ADAS cells have potential applications for the repair and regeneration of acute and chronically damaged tissues. Additional pre-clinical safety and efficacy studies will be needed before the promise of these cells can be fully realized.
White adipose tissue (WAT) is perhaps the most plastic organ in the body, capable of regeneration following surgical removal and massive expansion or contraction in response to altered energy balance. Research conducted for over 70 years has investigated adipose tissue plasticity on a cellular level, spurred on by the increasing burden that obesity and associated diseases are placing on public health globally. This work has identified committed preadipocytes in the stromal vascular fraction of adipose tissue and led to our current understanding that adipogenesis is important not only for WAT expansion, but also for maintenance of adipocyte numbers under normal metabolic states. At the turn of the millenium, studies investigating preadipocyte differentiation collided with developments in stem cell research, leading to the discovery of multipotent stem cells within WAT. Such adipose tissue-derived stem cells (ASCs) are capable of differentiating into numerous cell types of both mesodermal and nonmesodermal origin, leading to their extensive investigation from a therapeutic and tissue engineering perspective. However, the insights gained through studying ASCs have also contributed to more-recent progress in attempts to better characterize committed preadipocytes in adipose tissue. Thus, ASC research has gone back to its roots, thereby expanding our knowledge of preadipocyte commitment and adipose tissue biology.
Adipose stem cells represent a heterogenous population. Understanding the functional characteristics of subpopulations will be useful in developing adipose stem cell-based therapies for regenerative medicine applications. The aim of this study was to define distinct populations within the stromal vascular fraction based on surface marker expression, and to evaluate the ability of each cell type to differentiate to mature adipocytes.
Subcutaneous whole adipose tissue was obtained by abdominoplasty from human patients. The stromal vascular fraction was separated and four cell populations were isolated by flow cytometry and studied. Candidate perivascular cells (pericytes) were defined as CD146(+)/CD31(-)/CD34(-). Two CD31(+) endothelial populations were detected and differentiated by CD34 expression. These were tentatively designated as mature endothelial (CD31(+)/CD34(-)), and immature endothelial (CD31(+)/CD34(+)). Both endothelial populations were heterogeneous with respect to CD146. The CD31(-)/CD34(+) fraction (preadipocyte candidate) was also CD90(+) but lacked CD146 expression.
Proliferation was greatest in the CD31(-)/CD34(+) group and slowest in the CD146 group. Expression of adipogenic genes, peroxisome proliferator-activated receptor-γ, and fatty acid binding protein 4, were significantly higher in the CD31(-)/CD34(+) group compared with all other populations after in vitro adipogenic differentiation. This group also demonstrated the highest proportion of AdipoRed lipid staining.
The authors have isolated four distinct stromal populations from human adult adipose tissue and characterized their adipogenic potential. Of these four populations, the CD31/CD34(+) group is the most prevalent and has the greatest potential for adipogenic differentiation. This cell type appears to hold the most promise for adipose tissue engineering.
Autologous fat transplantation is frequently used for a variety of cosmetic treatments and difficult reconstructive indications such as involutional disorders, hemifacial atrophy, sequelae of radiation therapy, or similar problems. However, the limitations of fat transplantation are well known in such difficult cases, particularly the long-term unpredictability of volume maintenance. The ideal method of preparing autologous fat grafts optimizes tissue survival and reduces the variability of outcomes. We propose that enriching traditionally prepared fat grafts with adipose-derived regenerative cells (ADRCs) represents one such method.
Using a staged approach, we performed cell-enriched fat transfer by injecting autologous ADRCs into soft tissue that was recently grafted using traditional methods of fat transfer. Over a 3-year period, data were prospectively collected from 29 patients who underwent a single session of stem cell-enriched tissue injections (SET).
Cell-enriched grafts ranged in volume from 10 to 390 cc per recipient area and were obtained by manual or automated processes. The mean follow-up period was 10 months. Postoperative atrophy of the injected tissue was minimal and subjectively did not change after 8 weeks. Of note, historically reported rates of atrophy range from 20 to 80%. All patients were satisfied with the primary result with no need for a secondary session except for the cosmetic cases.
These preliminary results suggest that SET is safe and may provide superior results compared to traditional fat grafting. By performing the procedure in a staged approach, operating room expenses are minimized, which ultimately decreases the cost of the procedure. Adipose-derived regenerative cells may mitigate early ischemia by increasing angiogenesis, decreasing apoptosis, and modulating the local inflammatory response. This technique may be of particular value to the surgeon when grafting high volumes of fat or when faced with hostile recipient area conditions, including fibrosis and post radiation.
As the technique of autologous fat grafting is being refined and perfected, its clinical applications are expanding. The use of autologous fat grafting for primary breast augmentation is controversial due to a lack of clarity regarding its safety and efficacy. Most notably, concerns about interference with the detection of breast cancer have been raised, but these have not been clearly addressed in the literature. To help surgeons gain further insight, the authors conducted a systematic review of the literature, carefully comparing technique, clinical outcome, radiologic impact, and complications in all available data on this subject. Although an optimal method of autologous fat grafting for primary breast augmentation is yet to be standardized, further strong evidence-based studies are necessary to confirm the findings of this approach.
The purpose of this study was to determine the late decline in viability of fat cells over time for fat tissue stored at -15 degrees C and -70 degrees C after harvest from abdominal liposuction. A total of 16 females were recruited for this study. The viability of fat cell specimens was measured after freezing for 1, 3, 7, 14, 28, and 56 days. A number of viable mature adipocytes were evaluated by fluorescence microscopy after staining with fluorescein diacetate and propidium iodide. The glycerol-3-phosphate dehydrogenase activity was measured in lipoaspirates before digestion and the XTT reduction assay was performed. In addition, the XTT reduction assay was also performed on isolated lipocytes and preadipocytes.The viability of mature adipocytes was very low for both the -15 degrees C and -70 degrees C samples after 1 day of freezing (13.3% +/- 7.4% and 12.6% +/- 6.3%, respectively). There was no statistically significant difference between the samples stored at the 2 temperatures. The GPDH activity of the lipoaspirates frozen, for 1 day, at -15 degrees C and -70 degrees C was 25.1% +/- 10% and 28.7% +/- 11%, respectively. For the XTT test, the fractional enzyme activity of the lipoaspirates frozen, for 1 day, at -15 degrees C and -70 degrees C was 30.0% +/- 10.9% and 36.1% +/- 12.3%, respectively. In addition, the adipocytes had low activity from day one: 15.4% +/- 7.2% at -15 degrees C and 11.5% +/- 5.6% at -70 degrees C. Furthermore, the preadipocytes had a low activity of 8.0% +/- 6.0% at -15 degrees C and 8.6% +/- 3.8% at -70 degrees C. At 8 weeks, there were few viable mature adipocytes and the activity of the cells was very low by XTT and GPDH testing.The results of this study showed that the viability of adipocytes declined rapidly after frozen storage for 1 day at both -15 degrees C and -70 degrees C, and decreased gradually in storage after 8 weeks; at which time only approximately 5% of the fat cells were alive. These findings suggest that the present fat preservation storage techniques using a -15 degrees C freezer or a -70 degrees C deep freezer are both inadequate to maintain the viability of fat cells.
Isolation of adipose-derived stem cells (ASCs) typically involves 8+ hours of intense effort, requiring specialized equipment and reagents. Here, we present an improved technique for isolating viable populations of mesenchymal stem cells from lipoaspirate saline fractions within 30 minutes. Importantly, the cells exhibit remarkable similarities to those obtained using the traditional isolation protocols, in terms of their multipotent differentiation potential and immunophenotype. Reducing the acquisition time of ASCs is critical for advancing regenerative medicine therapeutics, and our approach provides rapid and simple techniques for enhanced isolation and expansion of patient-derived mesenchymal stem cells.
We found adult human stem cells that can generate, from a single cell, cells with the characteristics of the three germ layers. The cells are stress-tolerant and can be isolated from cultured skin fibroblasts or bone marrow stromal cells, or directly from bone marrow aspirates. These cells can self-renew; form characteristic cell clusters in suspension culture that express a set of genes associated with pluripotency; and can differentiate into endodermal, ectodermal, and mesodermal cells both in vitro and in vivo. When transplanted into immunodeficient mice by local or i.v. injection, the cells integrated into damaged skin, muscle, or liver and differentiated into cytokeratin 14-, dystrophin-, or albumin-positive cells in the respective tissues. Furthermore, they can be efficiently isolated as SSEA-3(+) cells. Unlike authentic ES cells, their proliferation activity is not very high and they do not form teratomas in immunodeficient mouse testes. Thus, nontumorigenic stem cells with the ability to generate the multiple cell types of the three germ layers can be obtained through easily accessible adult human mesenchymal cells without introducing exogenous genes. These unique cells will be beneficial for cell-based therapy and biomedical research.
Stem cell transplantation is expected to have good effects in the treatment of myocardial infarction (MI). We tested the effect of the transplantation of human adipose-derived cells (ASCs) in Sprague-Dawley (SD) rats with myocardial infarctions.
ASCs were isolated from the waste of elective abdominal surgery. The MI model was set up in SD rats by permanent ligation of the left anterior descending coronary artery. One week after MI, either 1 x 10(6) ASCs or an equal volume of phosphate-buffered saline (PBS) was injected into the infarct zone. Cardiac function was assessed by echocardiography, 1 day, 1 week, 2 weeks, and 4 weeks after treatment. Four weeks after transplantation, immunohistochemistry was performed.
Left ventricular function, including fractional shortening (FS), and ejection fraction (EF) showed a significant improvement in the ASCs transplantation group compared to the PBS group 4 weeks after treatment (p < 0.05). The anterior wall thickness of the left ventricle was significantly thicker in the ASCs transplantation group compared to the PBS group (p < 0.01). Multiple troponin T staining, and irregular, small amounts of connexin 43 expression also was observed in the ASCs transplantation group. Infarcted myocardium showed higher capillary density in the ASCs transplantation group than in the PBS injected group (p < 0.01).
This study provides encouraging evidence that transplantation of ASCs can improve cardiac function of infarct myocardium in rat models with a limitation of cardiac remodeling, improved wall thickness, and increased neovascularization.
In this study, we evaluated if the implantation of allogenic adipose-derived stem cells (ASCs) improved neurological function in a canine spinal cord injury model. Eleven adult dogs were assigned to three groups according to treatment after spinal cord injury by epidural balloon compression: C group (no ASCs treatment as control), V group (vehicle treatment with PBS), and ASC group (ASCs treatment). ASCs or vehicle were injected directly into the injured site 1 week after spinal cord injury. Pelvic limb function after transplantation was evaluated by Olby score. Magnetic resonance imaging, somatosensory evoked potential (SEP), histopathologic and immunohistichemical examinations were also performed. Olby scores in the ASC group increased from 2 weeks after transplantation and were significantly higher than C and V groups until 8 weeks (p < 0.05). However, there were no significant differences between the C and V groups. Nerve conduction velocity based on SEP was significantly improved in the ASC group compared to C and V groups (p < 0.05). Positive areas for Luxol fast blue staining were located at the injured site in the ASC group. Also, GFAP, Tuj-1 and NF160 were observed immunohistochemically in cells derived from implanted ASCs. These results suggested that improvement in neurological function by the transplantation of ASCs in dogs with spinal cord injury may be partially due to the neural differentiation of implanted stem cells.
The stromal vascular fraction (SVF) in adipose tissue contains a pool of various stem and progenitor cells, but the existence of hematopoietic stem and progenitor cells (HSPCs) in the SVF has not been seriously considered. We detected the presence of HSPCs in the SVF by phenotypically probing with Lin(-)Sca-1(+)c-kit(+) (LSK) and functionally confirming the presence using colony-forming cell assay and assessing the long-term multilineage reconstitution ability after SVF transplantation. The LSK population in the SVF was 0.004% plus or minus 0.001%, and 5 x 10(5) freshly isolated SVF cells gave rise to 13 plus or minus 4 multilineage colonies. In addition, 0.15% plus or minus 0.03% of SVF cells was home to bone marrow (BM), especially near vascular and endosteal regions, 24 hours after blood transplantation. SVF transplantation was capable of generating a long-term (> 16 weeks), but variable extent (2.1%-32.1%) multilineage reconstitution in primary recipients, which was subsequently transferred to the secondary recipients by BM transplantation. All HSPCs within the SVF originated from the BM. Furthermore, the granulocyte-colony-stimulating factor (G-CSF) mobilization of HSPCs from BM markedly elevated the number of phenotypic and functional HSPCs in the SVF, which induced a high efficiency long-term reconstitution in multilineage hematopoiesis in vivo. Our results provide compelling evidence that adipose tissue is a novel extramedullary tissue possessing phenotypic and functional HSPCs.
Over the last 30 years there has been interest in the use of autologous fat transplantation for breast reconstructive and cosmetic purposes. Up until now injection of adipose tissue into the breast has been subject to two limiting factors. First, fat injection into the breast could result in fat necrosis, cyst formation, and indurations that could be mistaken as cancerous calcifications. Second, the degree of reabsorption of the injected adipose tissue is unpredictable.
Patients included in the study were candidates for either breast reconstruction after tumor resection or breast augmentation and were divided into three groups. Group I included patients with asymmetry after mastectomy and breast reconstruction; Group II consisted of patients with congenital breast asymmetry; and Group III included patients requesting bilateral breast augmentation. All patients signed a consent form acknowledging potential complications of infiltrating fat into the breast.
A total of 820 consecutive female patients were operated on between 1983 and 2007. The age distribution of the patients ranged from 19 to 78 years, with a mean of 45.6 years. There were 381 patients in Group I, 54 in Group II, and 385 in Group III. Complications included ecchymosis in 76 patients, striae in 36 patients, 12 hematomas, and 5 infections. Long-term breast asymmetry was observed in 34 cases. Six hundred seventy patients have undergone mammography and ultrasonography 6 months and 1 year after their first intervention under our care. The majority of complications resulting from lipofilling of the breast have been seen in this series during the first 6 months after each session. Breast lesions, including calcifications, cysts, and cancer, that are not apparent in the first year after the final procedure of lipofilling we believe may not be directly associated with the autologous fat grafting to the breast. This has been confirmed by the long-term follow-up of 230 patients (range = 2-25 years, mean = 11.3 years) who have been followed up yearly with mammographic examination.
In the last 25 years the results of autologous fat transplantation have been predictable and satisfying on the condition that the treatment is performed in stages with small quantities of adipose tissue fat injected in each treatment session. To prevent major complications the final expected result should not be the aim of a single procedure. Mammary lipografting is a procedure that can be offered to patients for breast reconstructive and cosmetic purposes.
This article presents a specific method of autologous fatty tissue transplantation, Lipostructure, which incorporates the technique of syringe liposuction with an intricate layering of autologous fatty tissue. The presented methods of infiltration of fatty tissue allow precise control over the contours of the face to replace atrophied or missing structures and enhance facial contours. Autologous fatty tissue harvested, refined, and placed in the specific fashion described is presented as an exemplary agent for augmentation in soft-tissue facial recontouring.
There are a variety of recommended methods for harvesting, treating, and utilizing autologous fat grafts. Previous work with the MTT assay illustrated that various preimplantation handling techniques had minimal effect on the viability of fat samples. This assay was used to test the viability of harvested fat samples after being stored for up to 8 days in a variety of conditions. Surprisingly, freezing the fat before assaying also had no measurable detrimental effect, which led us to study this phenomenon in greater detail. The results demonstrated that fat stored at subzero temperatures showed remarkable maintenance of their mitochondrial metabolic activity as compared with fat stored in a 32 C incubator. These data suggest exciting possibilities for storage and banking of human adipose tissue, which would reduce patient cost, discomfort, and time associated with multiple grafting procedures.
Complications of autologous fat transfer (injection) include fat tissue embolization from injection in the glabellar and nasal regions. A rare complication is fat tissue e mbolization to the lung. The author reviews the literature of fat tissue embolization and reports a new case of embolization to the lung from fat transfer to the buttocks. The arterial and venous anatomy is discussed and the mechanisms of embolization are described.
Background: Adipose-derived mesenchymal stem cells (ADSC) may have a potential dual role in soft tissue augmentation by suppressing inflammation and promoting regeneration. Due to these properties, there is increasing interest in their potential use in autologous fat grafting, particularly to the breast.
Objectives: The authors isolate and compare ADSC derived from abdominal and breast tissues with a hypothesis that different adipose tissue sources may demonstrate different functional characteristics affecting outcomes in autologous cell transplantation in reconstructive and aesthetic surgery.
Methods: Adipose-derived mesenchymal stem cells from abdominal and breast tissues were isolated and compared in terms of surface marker expression, differentiation capabilities, and both fibroblast growth factor (FGF) and receptor expression. Immunophenotype of macrophages was also investigated using cell surface markers following a 7-day co-culture period with ADSC.
Results: Results showed similar cell surface phenotype and multilineage differentiation capabilities of ADSC derived from abdominal and breast tissues. Variations of FGF expression were demonstrated on reverse transcription polymerase chain reaction, with a significantly higher expression of FGF2 seen in breast ADSC. Following the 7-day co-culture period, increased expression of the anti-inflammatory surface marker CD206 was identified, with decreased CD16 and human leukocyte antigen–DR on macrophages co-cultured with ADSC compared with controls.
Conclusions: The data indicate similarities between ADSC derived from abdominal and breast tissues. Significant differences were seen, however, in the expression of FGF2, which is important in angiogenesis and wound healing. The results support the utility of ADSC in cell-based therapies such as autologous fat grafting.
The idea of autologous fat microtransplants has recently resurfaced because of interest by the press. Past experiments have shown that small amounts of fat may be transplanted with an expected survival rate between 10 and 50 percent without ectodermis. A great fund of knowledge exists showing that skin grafts will survive quite dependably if their thickness is up to about 0.0020 inch. For the first week or so, they live by diffusion and inosculation, and then neovascularization enables them to continue viability. I have developed a technique whereby fat is harvested through a blunt cannula with minimal vacuum to prevent explosion of the cellular fat globules. Fibrin and cellular debris are removed, and the fat globules are separated from the free fat, blood, and other constituents of the aspirate. Individual, free-floating 1- to 3-mm adipose fragments are then suspended in nutrient solution and injected through an 18-gauge needle. Multiple radial pathways, with each fat segment being separated from the other by host tissue, maximizes the host-prosthesis interface and the possibility for exchange of nutrients. I have attempted this procedure in more than 100 patients with widely varying results. In acne pits of the face, no significant improvement could be noted 6 weeks after injection. For the first few weeks, a near-perfect result was obtained, but none of these transplants in scarred areas of this kind have been of benefit. Injection of 10 to 50 cc in other areas has resulted in some cells (perhaps 10 percent) surviving over 2 years. I do not recommend autologous fat injection as a permanent transplant at this time, but I am continuing investigations to improve survival. An anonymous survey of the opinions of my patients shows a low regard by them for the results.
Background:
Nowadays, fat grafting is a widespread technique that is commonly used in plastic and reconstructive surgery. The classical fat-harvesting method in which a 10-cc syringe and a 3.0-mm cannula are used, may be time-consuming when a large quantity of adipose tissue is required. We describe a novel technique to optimize fat harvesting, the vacuum-assisted adipose tissue suction technique (VAST), in which disposable sterile components are used. This study compares the adipose tissue harvesting speed and the adipocyte volume between the VAST and the 10-cc-syringe technique.
Methods:
From May 2010 to May 2012, a total of 32 patients who had structural fat grafting for breast reconstruction were enrolled in this prospective study. In 16 patients (control group) fat was harvested by the classical 10-cc-syringe technique, and in the other 16 patients (VAST group) fat was harvested by the VAST. Adipose tissue was harvested from the abdomen area in all patients. The volume of harvested adipose tissue was noted every minute during the operative procedure. The operative harvesting speed was calculated for each patient after 5 min. The volume harvested in 5 min was centrifuged, and the remaining adipocyte volume was noted after centrifugation. The operative harvesting speed and the remaining adipocyte rate were compared in both groups.
Results:
The average volume of harvested adipose tissue was 18.1 ml in the control group and 156.2 ml in the VAST group (p < 0.001). The average harvesting speed was 3.6 ml/min in the control group using a 10-cc syringe and 31.2 ml/min in the VAST group (p < 0.001). The average remaining adipocyte volume, after centrifugation, was 13.5 ml in the control group, and 118.2 ml in the VAST group (p < 0.001). The average remaining adipocyte rate, after centrifugation, was 74.3 % in the control group and 75.4 % in the VAST group (p = 0.27).
Conclusions:
Adipose tissue harvesting can be optimized safely by using the VAST before structural fat grafting. Its quickness, low cost, and efficiency make us choose this method in breast reconstruction when a significant volume of adipocytes is required.
Level of evidence iii:
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Background:
Variability in harvest and processing technique may impact the success of fat grafting. This study compared properties of fat grafts produced by differing methods and assessed volume retention of the grafted tissue in a nude mouse model.
Methods:
In phase I, fat was harvested by either suction-assisted lipoaspiration or ultrasound-assisted lipoaspiration and then filtered using two different pore sizes. Graft material was analyzed for average parcel size; relative oil, fat, and aqueous fractions; and stromal vascular fraction yield. Filtrands and filtrates were injected into athymic nude mice. In phase II, lipoaspirate harvested by suction-assisted lipoaspiration only was processed by centrifugation, cotton gauze rolling, or filtration, and then studied in a similar manner.
Results:
Fat harvested by ultrasound- and suction-assisted lipoaspiration had comparable stromal vascular fraction counts and graft retention in vivo. Ultrasound-assisted lipoaspiration released only slightly more oil than suction-assisted lipoaspiration; filtering with either 500- or 800-µm pore size effectively removed fluid and oil. Centrifugation, cotton-gauze rolling, and filtration also effectively removed fluid and oil. In vivo graft retention and stromal vascular fraction yield was highest with the cotton gauze method. Histologic analysis of all explants showed intact adipose tissue.
Conclusions:
Ultrasound- and suction-assisted lipoaspiration yielded similar retention of fat grafts in a xenograft model. Processing with cotton gauze rolling may be best suited for grafting cosmetically sensitive areas of the body in which optimal retention is critical and lower total graft volumes are needed. Filtration and centrifugation both effectively removed fluid fractions and resulted in comparable graft retention, and are more feasible when larger volumes are required.
: Successful long-term volume retention of an autologous fat graft is problematic. The presence of contaminating cells, tumescent fluid, and free lipid in the graft contributes to disparate outcomes. Better preparation methods for the fat graft before transplantation may significantly improve results.
: Subcutaneous fat from 22 donors was divided and processed using various graft preparation methods: (1) no manipulation control, (2) gravity separation, (3) Coleman centrifugation, and (4) simultaneous washing with filtration using a commercially available system (Puregraft; Cytori Therapeutics, Inc., San Diego, Calif.). Fat grafts from various preparation methods were examined for free lipid, aqueous liquid, viable tissue, and blood cell content. Adipose tissue viability was determined by measuring glycerol release after agonist induction of lipolysis.
: All test graft preparation methods exhibited significantly less aqueous fluid and blood cell content compared with the control. Grafts prepared by washing with filtration exhibited significantly reduced blood cell and free lipid content, with significantly greater adipose tissue viability than other methods.
: Washing with filtration within a closed system produces a fat graft with higher tissue viability and lower presence of contaminants compared with grafts prepared by alternate methods.
Background:
Fat grafting has become routine in plastic surgery because of low donor-site morbidity, a low complication rate, and fast recovery time. The optimal technique, however, has yet to be defined. Two critical variables are pressure and shear, both defined as force divided by area. In this study, the authors examined the effect of pressure and shear on human fat grafts in a nude mouse model.
Methods:
For negative pressure, tumescent liposuction was performed on fresh panniculectomy specimens. Suction pressure was either -15 inHg or -25 inHg. Lipoaspirate was centrifuged at 1200 g and injected into the flanks of nude mice. For positive pressure, positive pressure was applied to lipoaspirate up to 6 atm for up to 3 minutes and then injected into nude mice. For shear stress, lipoaspirate was centrifuged at 1200 g for 3 minutes and then injected with a fast flow rate (3 to 5 cc/second) or slow flow rate (0.5 to 1 cc/second). After 4 weeks, the fat grafts were analyzed for weight and histology.
Results:
For negative pressure, there were no differences in weight or histology with high versus low suction pressures. For positive pressure, application of positive pressures up to 6 atm for up to 3 minutes did not create a significant difference in graft weight or histology at 4 weeks. For shear stress, in vivo, a slow injection pressure yielded a 38 percent increase in weight (p < 0.001) compared with fast injection. Histology was similarly affected.
Conclusions:
Higher aspiration pressures up to -0.83 atm did not affect fat graft viability in vivo. Positive pressure up to 6 atm also did not affect fat graft viability. The degree of shear stress, which is a function of flow rate, did significantly affect fat graft viability. Fat grafts injected slowly with low shear stress significantly outperformed fat injected with high shear stress. These data suggest that shear stress is a more important variable regarding fat graft viability than pressure.
Background:
Adipose tissue grafting is a promising method in the field of surgical filling. We studied the effect of centrifugation on fat grafts, and we propose an optimised protocol for the improvement of adipose tissue viability.
Methods:
Adipose tissue was subjected to different centrifugations, and the volumes of interstitial liquid and oil released were measured to choose the optimal condition. Tissue from this condition was then compared to tissue obtained from two traditional techniques: strong centrifugation (commonly 3 min at 3000 rpm/900 g), and decantation, by injecting into immunodeficient mice. The cytokine interleukin-6 (IL-6) and chemokine monocyte chemotactic protein-1 (MCP-1) were assayed 24 h post-injection, and after 1 month of grafting the state of the lipografts was evaluated through macroscopic and histological analysis, with oil gap area measurement.
Results:
Strong centrifugation (900 g, 1800 g) is deleterious for adipose tissue because it leads to until threefold more adipocyte death compared to low centrifugation (100 g, 400 g). In addition, mice injected with strong centrifuged and non-centrifuged adipose tissue have higher rates of blood IL-6 and MCP-1, compared to those grafted with soft centrifuged fat. Moreover, extensive lipid vacuoles were detectable on histological sections of the non-centrifuged lipografts, whereas lipografts from soft centrifugation contain a higher amount of connective tissue containing collagen fibres.
Conclusion:
It is necessary to wash and centrifuge adipose tissue before reinjection in order to remove infiltration liquid and associated toxic molecules, which in the long term are deleterious for the graft. However, strong centrifugation is not recommended since it leads very quickly to greater adipocyte death. Thus, soft centrifugation (400 g/1 min), preceded by washings, seems to be the most appropriate protocol for the reinjection of adipose tissue.
Over the past 20 years, there has been a dramatic increase in the use of autologous fat grafting to treat volume and contour defects in aesthetic and reconstructive surgery. It is generally accepted that fat grafting is safe, with good patient satisfaction. However, there are many procedural variations, and in terms of objective clinical effectiveness, the major disadvantage of this technique remains the unpredictable fat resorption rates and subsequent adverse events. Because of the rapidly evolving nature of this procedure, this review article provides an update on previous reviews by looking at the current evidence base regarding fat graft techniques and their effect on clinical outcome.
A systematic review of the scientific literature listed on PubMed was performed using 20 search terms focused on harvesting, processing, reinjection, and conservation of fat grafting. An evidence-based system was used to determine eligibility for clinical and preclinical studies.
Thirty-seven articles were selected based on inclusion and exclusion criteria: five articles were clinical trials and 32 were experimental comparative studies examining human fat grafting.
This systematic review revealed a lack of high-quality data despite the increase in fat grafting over the past 20 years. At present, there is no evidence that supports specific procedural standardization. Evidence-based studies that incorporate randomized controlled, prospective, multicenter trials are required to understand which factors influence positive fat grafting clinical outcomes.
Autologous fat transplantation is among the surgical procedures performed most commonly by plastic surgeons for cosmetic and/or reconstructive purposes. In the procedure, autologous fat is harvested and infiltrated during the same operation, and the success of this procedure relies on harvesting and transferring viable adipocytes. This study was designed to assess the histomorphometric characteristics and viability of the lipoaspirated cells that were harvested through different techniques.
This study enrolled 65 patients undergoing lipofilling for reconstructive purposes. Subcutaneous fat samples were collected manually through the wet and dry techniques using a two-hole Coleman blunt cannula attached to a 10-cc Luer-Lok syringe. Fat tissue preservation was assessed through conventional histomorphometry and a cell viability assessment, evaluating the mitochondrial function through the MTS CellTiter 96 Aqueous One Solution Assay (Promega Corp., Madison, Wis.).
No differences were observed between adipocyte samples harvested with or without tumescent solution. The morphometric analysis and adipocyte viability assessment confirmed the visual findings: the mean surface area and shape (circularity index) of the adipocytes were not significantly different in the lipoaspirate collected through the different techniques.
The results from the present study provide the first histologic evidence and cell viability assessment to demonstrate that there are no substantial differences in the adipose tissue specimens harvested with the wet and dry techniques.
Therapeutic, V.
Lipoaspirate centrifugation creates graded density of adipose tissue. High-density fat contains more vasculogenic cytokines and progenitor cells and has greater graft survival than low-density fat. The authors hypothesize that accelerating the bone marrow-derived progenitor cell response to injected low-density fat will improve its graft survival.
Male 8-week-old FVB mice (n=60) were grafted with either high-density (n=20) or low-density (n=40) human lipoaspirate. Half of the mice receiving low-density fat (n=20) were treated with a stem cell mobilizer for 14 days. Grafted fat was harvested at 2 and 10 weeks for analysis.
Low-density fat, low-density fat plus daily AMD3100, and high-density fat had 26±3.0, 61.2±7.5, and 49.6±3.5 percent graft survival, respectively, at 2 weeks (low-density fat versus low-density fat plus daily AMD3100 and low-density fat versus high-density fat, both p<0.01). Similar results were observed 10 weeks after grafting. Mice receiving low-density fat plus daily AMD3100 had significantly more vasculogenic progenitor cells per cubic centimeter of peripheral blood (p<0.01) and more new blood vessels (p<0.01). Both low-density fat plus daily AMD3100 and high-density fat contained more stromal-derived factor-1α and vascular endothelial growth factor mRNA/protein.
Endogenous progenitor cell mobilization enhances low-density fat neovascularization, increases vasculogenic cytokine expression, and improves graft survival to a level equal to that of high-density fat grafts.
Cited By (since 1996): 7, Export Date: 27 September 2011, Source: Scopus
Recently, adipose tissue harvested by liposuction has been identified as a source of processed lipoaspirate cells. The aim of this study was to determine the concentration of processed lipoaspirate cells in adipose tissue obtained by liposuction from different harvest areas in women.
A prospective cross-sectional study was conducted in 25 women in whom liposuction in four or more different zones in the same procedure was indicated. After selective liposuction, the material was sent to the laboratory, where it was processed for extraction of processed lipoaspirate cells, which were separated from the adipose tissue, quantified, and characterized through determination of c-kit expression. The following harvest regions were evaluated: upper abdomen, lower abdomen, trochanteric region, inner thigh, knee, and flank. The cell concentration obtained at each site was compared by analysis of variance for mixed models.
A significant difference was found for cell concentration obtained at the different harvest sites. The cell concentration in the lower abdomen was greater than in other areas, but no significant difference was found in relation to the inner thigh.
The lower abdomen and the inner thigh may have higher processed lipoaspirate cell concentrations. These sites may turn out to be better sources of adult mesenchymal stem cells.
Although the increasing trend is to rebuild facial soft-tissue volume with autologous fat transfer, there is no agreement concerning the best way of processing the harvested fat before reinjecting it. Among all the reported fat graft processing techniques, in the present study, the authors compared the clinical results obtained using simple filtered and washed fat with those achieved by means of pure centrifuged fat.
A prospective double-blind study was conducted on 25 healthy patients undergoing facial fat transplantation from January of 2006 to June of 2006. During the same session, half the face was injected with simple filtered and washed fat, and the other half was instead treated with centrifuged fat. Subjective and objective methods were used to evaluate the results. The subjective methods included a questionnaire, sent to all patients, accompanied by an explanatory letter. The objective method involved the evaluation of preoperative and postoperative photographs by a three-member jury. The average follow-up period was 12 months.
The authors' experimental work demonstrates that there was no significant difference between the two fat-processing techniques. In the long term, the implanted hemifacial regions produced comparable results.
The authors, following their personal experience based on the reported data, went back to using the simple filtered fat after some years of use of centrifuged fat.
Breast implant reconstruction after radiotherapy carries a high risk of failure and complication. Nevertheless, it may be the only alternative for patients who are not suitable for autologous reconstruction or who refuse this option. As clinical and experimental studies have demonstrated that grafting adipose tissue (lipofilling) in an irradiated area improves the quality of the skin, we made the assumption that preliminary fat grafting of the chest wall might reduce the complication and failure rates of implant reconstruction by improving the implant coverage.
From 2007 to 2009, 28 patients had fat transfer to the chest wall, prior to implant reconstruction. All patients had had mastectomy and irradiation for breast cancer. Lipofilling was initiated 6 months after the end of radiotherapy. The mean number of fat-grafting sessions was 2 (range 1-3). An average volume of 115 cc (70-275 cc) was injected each time. Once the chest wall's skin seemed to have gained enough thickness, implant reconstruction was performed.
The mean follow-up period was 17 months. Three minor complications occurred. Implant explantation was performed in one case for exposition. The cosmetic results were good and very good in >80% of the cases.
This study points out the benefits of fat grafting to the irradiated chest wall prior to implant placement and demonstrates that lipofilling prepares the ground to implant breast reconstruction. This approach could be considered as an alternative to flap reconstruction for selected patients.
Based on the analysis of exudates from injured adipose tissue, we prepared a mixture containing the injury-associated growth factors at the same proportion as the exudates, named adipose injury cocktail (AIC). We hypothesized that AIC induces a series of regenerating and angiogenic processes without actual wounding. The purpose of this study is to elucidate the therapeutic potentials of AIC. AIC preferentially activated adipose-derived stem/progenitor/stromal cells (ASCs) to proliferate, migrate, and form networks compared with vascular endothelial cells, whereas vascular endothelial growth factor did not induce mitogenesis or chemotaxis in human ASCs. Each component growth factor of AIC was differently responsible for the ASC activation. AIC-treated ASCs tended to differentiate into adipocytes or vessel-constituting cells rather than into other cell types. In ischemic adipose tissues of mice, induced by either a surgical intervention or diabetes, AIC administration enhanced proliferation, especially of CD31(-)/CD34(+) ASCs, and mitigated tissue hypoxia by increasing capillary density and reducing fibrogenesis. These results suggest that AIC may have therapeutic potentials for various ischemic/hypoxic conditions by inducing adipose remodeling and neovascularization through activation of ASCs and other cells. Treatment with AIC has many advantages over cell-based therapies regarding morbidity, cost, and physical risks and may be used as an alternative therapy for improving tissue oxygen.
The authors investigated the use of serial autologous fat grafting to restore soft-tissue contour in craniofacial microsomia patients.
Patients with moderate to severe craniofacial microsomia were divided into two groups. Microvascular free flap patients had reconstruction with inframammary extended circumflex scapular flaps at skeletal maturity (n = 10). Alternatively, patients had fat grafting during multiple staged operations for mandible and ear reconstruction (n = 21). Sex, age, severity of deformity [determined by OMENS (orbital deformity, mandibular hypoplasia, ear deformity, nerve involvement, and soft-tissue deficiency) classification], number of procedures, operative times, and augmentation volumes were recorded. A digital three-dimensional photogrammetry system was used to determine "final fat take" and symmetry (affected side versus unaffected side). Physician and patient satisfaction were elicited.
Microvascular free flap and fat grafting groups had similar OMENS scores, 2.4 and 2.3, and similar mean prereconstruction symmetry scores, 74 percent and 75 percent, respectively. Although the mean number of procedures was less for the microvascular free flap group versus the fat grafting group (2.2 versus 4.3), the combined surgical time was greater for the microvascular free flap group. The complication rate for the microvascular free flap group was 12 percent and that for the fat grafting group was 5 percent. The mean microvascular free flap volume implanted was 131 cc, with a final measured volume of 106 cc. Mean fat grafting volume injected per case was 33 cc, with total fat injections of 146 cc and a final measured volume of 121 cc. There was a mean fat loss of 25 cc and 83 percent fat take. Symmetry score was 121 percent for the microvascular free flap group and 99 percent for the fat grafting group. No statistically significant difference in patient or physician satisfaction was noted.
Serial fat grafting provided a useful alternative to microvascular free tissue transfer after skeletal reconstruction.
To investigate the effect of adipose stromal vascular fraction cells (SVFs) on the survival rate of fat transplantation.
0. 5 ml autologous fat tissue was mixed with: 1) Di-labeled autologous SVFs ( Group A); 2) Di-labeled autologous adipose-derived stem cells (ASCs) (Group B); 3)Complete DMEM (Group C). And then the mixture was injected randomly under the back skin of 14 rabbits. The transplanted fat tissue in three groups was harvested at 6 months after implantation. Wet weight of fat grafts was measured for macroscopic aspects. After HE staining, blood vessel density, viable adipocytes and fibrous proliferation were counted respectively for histological evaluation. Trace of DiI-labeled ASCs in vivo was detected by fluorescent microscope.
The wet weight of fat grafts in group A (291.0 +/- 72.1) mg and group B (269.3 +/- 67.3) mg was significantly higher than that in group C (177.8 +/- 60.0) mg, but the difference between Group A and Group B was not significant. Histological analysis revealed that the fat grafts in group A and B was consisted predominantly of adipose tissue with less fat necrosis and fibrosis, compared with the fat grafts in group C. The grafts in both group A and B had significantly higher capillary density than those in the control group. Part of vascular endothelial cells were observed to origin from ectogenic DiI-labeled SVFs and ASCs.
The autologous isolated SVFs has a similar effect as autologous cultured ASCs to improve the survival rate of fat transplantation. And the former is more practical and safe, indicating a wide clinical application in the future.
Autologous fat transplantation is a well-established technique in surgery. Moreover, the use of preadipocytes in soft-tissue engineering is currently being intensely investigated. Current efforts focus on identifying maneuvers that may minimize resorption and provide predictable late results. The aim of this study was to investigate the influence of different local anesthetics frequently used in clinical practice on the viability of preadipocytes and their ability to differentiate into adipocytes.
Human preadipocytes were isolated from subcutaneous adipose tissue of 15 patients and treated with bupivacaine, mepivacaine, ropivacaine, articaine/epinephrine, and lidocaine for 30 minutes. Viability was determined directly after treatment and during the ensuing cultivation. Differentiation of preadipocytes was determined by expression of the adipocyte marker adiponectin.
Although the immediate effects of mepivacaine and ropivacaine were only moderate, treatment with articaine/epinephrine and lidocaine strongly impaired preadipocyte viability. Cells normally attached to the culture dishes and proliferated irrespective of the previous treatment. During long-term cultivation, articaine/epinephrine-treated cell viability decreased markedly, whereas other local anesthetics had no impact. Despite normal phenotypic appearance of cells treated with bupivacaine, mepivacaine, ropivacaine, and lidocaine, all local anesthetics markedly impaired adipocyte differentiation as determined by adiponectin expression.
The authors' results show that there is a marked influence of local anesthetics not only on the quantity but also on the quality of viable preadipocytes as determined by their ability to differentiate into mature adipocytes. Therefore, these results should be considered in the context of autologous fat transfer and soft-tissue engineering.
Because of their multi/pluripotency and immunosuppressive properties mesenchymal stem/stromal cells (MSCs) are important tools for treating immune disorders and for tissue repair. The increasing use of MSCs has led to production processes that need to be in accordance with Good Manufacturing Practice (GMP). In cellular therapy, safety remains one of the main concerns and refers to donor validation, choice of starting material, processes, and the controls used, not only at the batch release level but also during the development of processes. The culture processes should be reproducible, robust, and efficient. Moreover, they should be adapted to closed systems that are easy to use. Implementing controls during the manufacturing of clinical-grade MSCs is essential. The controls should ensure microbiological safety but also avoid potential side effects linked to genomic instability driving transformation and senescence or decrease of cell functions (immunoregulation, differentiation potential). In this rapidly evolving field, a new approach to controls is needed.
The efficient harvest of abundant viable adipocytes for grafting is of considerable interest. Hand aspiration, low-g-force, short-duration centrifugation, and harvest of the lower sublayer of fat centrifugate maximize viable adiopocytes, but this process is cumbersome with conventional equipment. The Lipose Corporation (Greenwich, Conn.) has produced special syringes, filters, and a low-g-force centrifuge (Viafill system) to facilitate this process. The adipocyte viability using this system is presented.
Six women underwent fat graft harvest using the Viafill system from the lower hips (n = 6) and/or upper hips (n = 3). After centrifugation for 2 minutes at 50 g, the lower, middle, and top sublayers of the adipose layer were analyzed for viable adipocyte counts using trypan blue vital staining. Additional samples from standard power-assisted liposuction were obtained and analyzed similarly.
The mean difference in square-root transformation of cell counts between the bottom sublayer of centrifuged fat and the middle sublayer was 0.95 (95 percent CI, 0.61 to 1.3), and the difference between the middle and top sublayers was 0.67 (CI, 0.50 to 0.84). Thus, the bottom sublayer had approximately 2.5 to 3 times more cells than the top sublayer. The difference between the hand aspirate samples and the power-assisted liposuction samples was significant (1.62; CI, 1.35 to 1.90).
This study reconfirms the authors' early findings that atraumatic harvest of lipoaspirate yields high cell counts and that adipocyte density is greatest at the lowest sublayer of centrifuged fat. The Viafill system provides a more efficient and user-friendly system for fat grafting while maintaining cell counts similar to the authors' technique using conventional equipment.
Standard protocols for autologous fat transfer involve centrifugation of the lipoaspirate for better separation. The effect of the centrifugal forces on cell viability and possible induction of apoptosis is discussed controversially in current literature. We have examined the vitality of adipocytes in lipoaspirates after centrifugation by 8 different accelerations up to 20.000g immediately after the respective centrifugation as well as 4 days later by staining. No significant alterations in the viability of differently centrifuged adipocytes were found. Cultivation of the samples after centrifugation revealed no apoptotic changes. Our results show that centrifugation, as a part of the protocol of lipofilling, has no effect on the survival rate of isolated adipocytes in the purified fat. In contrast, lipoaspirates centrifuged with higher accelerations seem to be better cleansed of oil and cell debris than samples treated with lower centrifugal forces.
Because adipose-tissue-derived stromal cell (ADSC) is readily accessible and abundant in stem cell, ADSC may be a better candidate for cell therapy and tissue engineering. This study investigated the potential of ADSC implantation to restore disc in a rat IVD model.
The first coccygeal disc segments of a Sprague-Dawley rat was left undamaged as a control (NC) group, and other two segments were damaged by needle injection. Two weeks later, ADSCs (TS) group or saline (IN) group was transplanted into each of the two damaged segments.
At 6 weeks after transplantation, the TS group showed a significantly smaller reduction in disc height than the IN group and exhibited a restoration of MRI signal intensity. Hematoxylin and eosin staining revealed a greater restoration of the inner annulus structure in the TS group. Anti-Human Nucleic Antibody, collagen type II, and aggrecan, staining showed positive findings at 2 weeks after transplantation in TS group.
ADSCs show potential for restoring degenerative discs and may prove effective in the treatment of IVD.
Centrifugation is one of the preferred methods of fat processing. Although it has been promoted for nearly three decades to separate adipose tissue components before grafting, there remain many controversies regarding the results obtained with centrifuged adipose tissue.
The authors demonstrate the effects of centrifugation on the cellular components of aspirated fat.
Fat harvested from the lower abdomen of 10 female patients undergoing liposuction was divided in two equal parts, then processed by decantation or centrifugation and sent to the laboratory. Each processed lipoaspirate was analyzed histologically after hematoxylin and periodic acid-Schiff staining for the presence of intact adipocytes. It was then cultured and analyzed by multicolor flow cytometry for identification of adipose-derived mesenchymal stem cells.
The middle layer of the centrifuged lipoaspirate, which is used by many surgeons, showed a great majority of altered adipocytes and very few mesenchymal stem cells in comparison with the decanted sample, which maintained the integrity of the adipocytes and showed a greater number of mesenchymal stem cells. The pellet observed as a fourth layer at the bottom of the centrifuged lipoaspirate showed the greatest concentration of endothelial cells and mesenchymal stem cells, which play a crucial role in the angiogenic and adipogenic effect of the grafted tissue.
If centrifuged lipoaspirate is used, the pellet (rich in adipose-derived mesenchymal stem cells) and the middle layer should be employed to increase fat graft survival.
The viability of fat grafts harvested with an established technique after cryopreservation remains unknown. This study was conducted in vitro to evaluate the viability of autologous fat grafts harvested with the Coleman technique and subsequently preserved with our preferred cryopreservation method. Eight adult females were enrolled in this study. In each patient, 10 mL of fat grafts were harvested with the Coleman technique by a single surgeon from the lower abdomen. In group 1, 5 mL of fresh fat grafts were mixed with cryoprotective agents and underwent cryopreservation with controlled slow cooling and fast rewarming. In group 2, 5 mL of fresh fat grafts without cryopreservation from the same patient served as a control. The fat graft samples from both groups were evaluated with trypan blue vital staining, glycerol-3-phophatase dehydrogenase assay, and routine histology. Viable adipocyte counts were found similar in both group 1 and group 2 (3.46 +/- 0.91 vs. 4.12 +/- 1.11 x 10/mL, P = 0.22). However, glycerol-3-phophatase dehydrogenase activity was significantly lower in group 1 compared with group 2 (0.47 +/- 0.09 vs. 0.66 +/- 0.09 u/mL, P < 0.001). Histologically, the normal structure of fragmented fatty tissues was found primarily in both groups. Our results indicate that autologous fat grafts harvested with the Coleman technique and preserved with our preferred cryopreservation method have a normal histology with near the same number of viable adipocytes as compared with the fresh fat grafts. However, those cryopreserved fat grafts appear to have a less optimal level of adipocyte specific enzyme activity compared with the fresh ones and thus may not survive well after they are transplanted without being optimized.
The in vivo progenitor of culture-expanded mesenchymal-like adipose-derived stem cells (ADSC) remains elusive, owing in part to the complex organization of stromal cells surrounding the small vessels, and the rapidity with which adipose stromal vascular cells adopt a mesenchymal phenotype in vitro. Immunohistostaining of intact adipose tissue was used to identify three markers (CD31, CD34, and CD146), which together unambiguously discriminate histologically distinct inner and outer rings of vessel-associated stromal cells, as well as capillary and small vessel endothelial cells. These markers were used in multiparameter flow cytometry in conjunction with stem/progenitor markers (CD90 and CD117) to further characterize stromal vascular fraction (SVF) subpopulations. Two mesenchymal and two endothelial populations were isolated by high speed flow cytometric sorting, expanded in short term culture, and tested for adipogenesis. The inner layer of stromal cells in contact with small vessel endothelium (pericytes) was CD146+/alpha-SMA+/CD90+/-/CD34-/CD31-; the outer adventitial stromal ring (designated supra adventitial-adipose stromal cells, SA-ASC) was CD146-/alpha-SMA-/CD90+/CD34+/CD31-. Capillary endothelial cells were CD31+/CD34+/CD90+ (endothelial progenitor), whereas small vessel endothelium was CD31+/CD34-/CD90- (endothelial mature). Flow cytometry confirmed these expression patterns and revealed a CD146+/CD90+/CD34+/CD31- pericyte subset that may be transitional between pericytes and SA-ASC. Pericytes had the most potent adipogenic potential, followed by the more numerous SA-ASC. Endothelial populations had significantly reduced adipogenic potential compared with unsorted expanded SVF cells. In adipose tissue, perivascular stromal cells are organized in two discrete layers, the innermost consisting of CD146+/CD34- pericytes, and the outermost of CD146-/CD34+ SA-ASC, both of which have adipogenic potential in culture. A CD146+/CD34+ subset detected by flow cytometry at low frequency suggests a population transitional between pericytes and SA-ASC.
In the last decade, controversy has arisen regarding the influence of fat harvesting, processing and injection techniques on adipose tissue graft. The aim of this study is to compare the influence of three widely used fat processing techniques in plastic surgery on the viability and number of adipocytes and mesenchymal stem cells (MSCs) of aspirated fat.
A prospective cross-sectional study was conducted in 20 adult healthy female patients in whom material obtained by liposuction of the lower abdomen was separated and processed by decantation, washing or centrifugation. The morphology and quantity of adipocytes were determined by histological analysis. The viability and number of MSCs in the middle layer of each lipoaspirate and the pellet derived from centrifuged samples were obtained by multi-colour flow cytometry.
Cell count per high-powered field of intact nucleated adipocytes was significantly greater in decanted lipoaspirates, whereas centrifuged samples showed a greater majority of altered adipocytes. MSC concentration was significantly higher in washed lipoaspirates compared to decanted and centrifuged samples. However, the pellet collected at the bottom of the centrifuged samples showed the highest concentration of MSCs.
Based on the theory of cell survival stating the importance of adipocytes' integrity for graft survival and the theory claiming the importance of regenerative MSCs in the maintenance and stabilisation of fat transplant, washing may turn out to be the best processing technique for adipose tissue graft take. While eliminating most contaminants during the process, it preserved and maintained the quantity, integrity and viability of the most important components of aspirated adipose tissue.
Mesenchymal stem cells (MSCs) represent a promising therapeutic approach for neurological autoimmune diseases; previous studies have shown that treatment with bone marrow-derived MSCs induces immune modulation and reduces disease severity in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Here we show that intravenous administration of adipose-derived MSCs (ASCs) before disease onset significantly reduces the severity of EAE by immune modulation and decreases spinal cord inflammation and demyelination. ASCs preferentially home into lymphoid organs but also migrates inside the central nervous system (CNS). Most importantly, administration of ASCs in chronic established EAE significantly ameliorates the disease course and reduces both demyelination and axonal loss, and induces a Th2-type cytokine shift in T cells. Interestingly, a relevant subset of ASCs expresses activated alpha 4 integrins and adheres to inflamed brain venules in intravital microscopy experiments. Bioluminescence imaging shows that alpha 4 integrins control ASC accumulation in inflamed CNS. Importantly, we found that ASC cultures produce basic fibroblast growth factor, brain-derived growth factor, and platelet-derived growth factor-AB. Moreover, ASC infiltration within demyelinated areas is accompanied by increased number of endogenous oligodendrocyte progenitors. In conclusion, we show that ASCs have clear therapeutic potential by a bimodal mechanism, by suppressing the autoimmune response in early phases of disease as well as by inducing local neuroregeneration by endogenous progenitors in animals with established disease. Overall, our data suggest that ASCs represent a valuable tool for stem cell-based therapy in chronic inflammatory diseases of the CNS.
Mesenchymal Stem Cells/Multipotent Marrow Stromal Cells (MSC) are multipotent adult stem cells present in all tissues, as part of the perivascular population. As multipotent cells, MSCs can differentiate into different tissues originating from mesoderm ranging from bone and cartilage, to cardiac muscle. Conflicting data show that MSCs could be pluripotent and able to differentiate into tissues and cells of non-mesodermic origin as neurons or epithelial cells. Moreover, MSCs exhibit non-HLA restricted immunosuppressive properties. This wide range of properties leads to increasing uses of MSC for immunomodulation or tissue repair. Based on their immunosuppressive properties MSC are used particularly in the treatment of graft versus host disease, For tissue repair, MSCs can work by different ways from cell replacement to paracrine effects through the release of cytokines and to regulation of immune/inflammatory responses. In regenerative medicine, trials are in progress or planed for healing/repair of different tissue or organs as bone, cartilage, vessels, myocardium, or epithelia. Although it has been demonstrated that ex-vivo expansion processes using fetal bovine serum, recombinant growth factors (e.g. FGF2) or platelet lysate are feasible, definitive standards to produce clinical-grade MSC are still lacking. MSCs have to be produced according GMP and regulation constraints. For answering to the numerous challenges in this fast developing field of biology and medicine, integrative networks linking together research teams, cell therapy laboratories and clinical teams are needed.
The purpose of this study was to analyze the role of fat grafting for restoration of facial contour deformities (volumes) in traumatic and malformation cases. Outcomes were evaluated for each facial aesthetic subunit to demonstrate the role of the recipient site. An algorithm for the treatment of facial malformations and traumatic sequelae by subunits, in relation to the results obtained in this study, is proposed.
This retrospective study involved 100 patients treated by structural fat grafting of the facial region. Results were evaluated by a subjective self-evaluation survey (i.e., a questionnaire answered by patients) and an objective assessment by a five-member jury. Each subunit of the face was studied separately. Results were presented separately and compared.
The average follow-up period was 23 months. The overall satisfaction rate of patients was 74 percent. The average score for subjective evaluation was 14.5 of 20. The objective score was 13.9 of 20. The results were significantly different depending on the aesthetic subunit of the face. The best results were achieved in the malar (89 percent good results) and lateral cheek areas (84 percent good results). The poorest results were registered for the lower and upper lip areas (34 percent and 31 percent good results, respectively). Minor complications were observed in 3 percent of the cases.
Fat tissue grafting is a simple, efficient, and reproducible technique for restoration of facial volumes. In the absence of functional disorders, it is the authors' first choice in the decision-making process for the treatment of facial soft-tissue deficiencies.
Autologous fat grafting has become a workhorse for soft-tissue augmentation throughout the body. In the reconstructed breast, autologous fat grafting is a useful tool for managing secondary contour deformities. The authors have categorized these deformities into three types: type 1 deformities are step-off deformities between the chest wall/reconstructed breast interface, type 2 deformities result from intrinsic deficiencies within a flap such as fat necrosis, and type 3 deformities are the result of extrinsic factors such as postoperative irradiation.
The authors conducted a detailed retrospective review of 110 patients who have received fat grafting to the reconstructed breast for the management of contour deformities. In addition, the authors reviewed the recent literature describing the use of autologous fat grafting to the breast. Particular attention has been placed on the concerns of oncologic surveillance in reconstructed breasts that have undergone fat grafting.
The authors have had relative success in the treatment of patients who will require postoperative irradiation and even those who have rippling surrounding an implant.
Autologous fat grafting represents an important tool for the management of secondary contour deformities of the reconstructed breast. Fat grafting is a simple, safe, and effective treatment option, with low morbidity.