No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Education and Understanding Orthobiologics: Then and Now
Abstract
Over the past 10 years, the field of Orthobiologics has grown rapidly and started to establish a foundation as a potentially safe and efficacious alternative for a variety of musculoskeletal injuries, including joint disorders such as osteoarthritis and chronic tendinopathy. With life expectancy on the rise, and an aging population of baby boomers, the demand for viable minimally invasive options is at an all-time high. The increased demand has led to scores of physicians attempting to integrate regenerative options into their practices. However, as the exponential growth of orthobiologics continues to skyrocket, coordinated research efforts haven’t been able to match the same trajectory, resulting in a paucity of high level of evidence studies. As the volume of physicians utilizing orthobiologics continues to rise, we have a duty as innovators in the field to strive for cohesiveness and standardization to provide the highest level of safety and therapeutic efficacy for patients. In order to satisfy this responsibility and progress the field of orthobiologics, it is important to establish a common definition and understanding of current orthobiologic options, as well as improve access to continuing education and facilitate research collaboration throughout the global medical community.
... The field of orthobiologics is growing rapidly, regarding both its clinical application and the pace of relevant scientific discovery [10]. It is important to reflect on the origins and current state of the field to shape its future direction more effectively. ...
- Knee pathologies including focal cartilage injuries, osteoarthritis (OA), and ligament injuries are common. The poor regeneration and healing potential of cartilage has led to the search for other treatment modalities with improved healing capacity. Furthermore, with an increasing elderly population that desires to remain active, the burden of knee pathologies is expected to increase. Increased sports participation and the desire to return to activities faster is also demanding more effective and minimally invasive treatment options. Thus, the use of biologic agents in the treatment of knee pathologies has emerged as a potential option. Despite the increasing use of biologic agents for knee pathology, there are conflicting results on the efficacy of these products. Furthermore, strong data supporting the optimal preparation methods and composition for widely used biologic agents, such as platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC), largely remain absent from the literature. This review presents the literature on the most commonly employed biologic agents for the different knee pathologies.
Objective: This study aims to evaluate the clinical effects of Platelet Rich Plasma (PRP) and Hyaluronic Acid (HA) as individual treatments for mild to moderate Osteoarthritis (OA), and also examine the potential synergistic effects of PRP in combination with HA. Research continues to emerge examining the potential therapeutic efficacy of HA and PRP as autologous injectable treatments for joint arthritis. However, there is a paucity of research investigating the effects of combining HA and PRP on pain and functional status in patients with OA.
Design: In this multicenter, randomized, controlled, double blind, prospective trial, 105 patients with mild to moderate knee osteoarthritis who met the study criteria were randomly allocated to one of three interventions: HA (n=36), PRP (n=36), or HA+PRP (n=33). Each patient received 3 intaarticular knee injections of their assigned substance, with 2 week intervals between each injection. Clinical outcomes were evaluated using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Visual Analogue Scale (VAS) questionnaire at baseline and after 1,3,6, and 12 months.
Results: The study showed that the PRP group have significant reduction in VAS scores at 1 (p= 0.003), 3 (p= 0.0001), 6 (p= 0.0001) and 12 (p= 0.000) months when compared to HA. In addition, the PRP group illustrated greater improvement in WOMAC physical activity scale at 12 months (p= 0.008) when compared to the HA group. Combining HA and PRP resulted in a significant decreases in pain (p=0.0001) and functional limitation (p=0.0001) when compared to HA alone at 1 year post treatment; and significantly increased physical function at 1 (p=0.0004) and 3 (p=.011) months when compared to PRP alone.
Conclusion: The findings of the study support the use of autologous PRP as an effective treatment of mild to moderate knee osteoarthritis. It also shows that the combination of HA and PRP resulted to better outcomes than HA alone up to 1 year and PRP alone up to 3 months. Furthermore, the results suggest that combination of PRP and HA could potentially provide better functional outcomes in the first 30 days after treatment with both PRP and HA alone.
Tissue engineering using mesenchymal stem cells holds great promise for regenerating critically sized bone defects. While the bone marrow-derived mesenchymal stem cell (MSC) is the most widely studied stromal/stem cell type for this application, its rarity within bone marrow and painful isolation procedure have motivated investigation of alternative cell sources. Adipose-derived stromal/stem cells (ASCs) are more abundant and more easily procured; furthermore, they also possess robust osteogenic potency. While these two cell types are widely considered very similar, there is a growing appreciation of possible innate differences in their biology and response to growth factors. In particular, reports indicate that their osteogenic response to platelet-derived growth factor BB (PDGF-BB) is markedly different: MSCs responded negatively or not at all to PDGF-BB while ASCs exhibited enhanced mineralization in response to physiological concentrations of PDGF-BB. In this study, we directly tested whether a fundamental difference existed between the osteogenic responses of MSCs and ASCs to PDGF-BB. MSCs and ASCs cultured under identical osteogenic conditions responded disparately to 20 ng/mL of PDGF-BB: MSCs exhibited no difference in mineralization while ASCs produced more calcium per cell. siRNA-mediated knockdown of PDGFRβ within ASCs abolished their ability to respond to PDGF-BB. Gene expression was also different; MSCs generally downregulated and ASCs generally upregulated osteogenic genes in response to PDGF-BB. ASCs transduced to produce PDGF-BB resulted in more regenerated bone within a critically sized murine calvarial defect compared to control ASCs, indicating PDGF-BB used specifically in conjunction with ASCs might enhance tissue engineering approaches for bone regeneration. This article is protected by copyright. All rights reserved.
© 2015 AlphaMed Press.
Leukocyte-poor platelet-rich plasma (LP-PRP) is hypothesized to be more suitable for intra-articular injection than leukocyte-rich PRP (LR-PRP) in the treatment of knee osteoarthritis.
To compare clinical outcomes and rates of adverse reactions between LP-PRP and LR-PRP for this application.
Meta-analysis.
The MEDLINE, EMBASE, and Cochrane databases were reviewed. The primary outcome was the incidence of local adverse reactions. Secondary outcomes were the changes in International Knee Documentation Committee (IKDC) subjective score and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score between baseline and final follow-up measurements. A Bayesian network meta-analysis was performed, with a post hoc meta-regression to correct for baseline differences in WOMAC scores. Treatment rankings were based on surface under the cumulative ranking (SUCRA) probabilities.
Included in the analysis were 6 randomized controlled trials (evidence level 1) and 3 prospective comparative studies (evidence level 2) with a total of 1055 patients. Injection of LP-PRP resulted in significantly better WOMAC scores than did injection of hyaluronic acid (mean difference, -21.14; 95% CI, -39.63 to -2.65) or placebo (mean difference, -17.84; 95% CI, -34.95 to -0.73). No such difference was observed with LR-PRP (mean difference, -14.28; 95% CI, -44.80 to 16.25). All treatment groups resulted in equivalent IKDC subjective scores. The SUCRA analysis showed that LP-PRP was the highest ranked treatment for both measures of clinical efficacy (WOMAC and IKDC). Finally, PRP injections resulted in a higher incidence of adverse reactions than hyaluronic acid (odds ratio, 5.63; 95% CI, 1.38-22.90), but there was no difference between LR-PRP and LP-PRP (odds ratio, 0.78; 95% CI, 0.05-11.93). These reactions were nearly always local swelling and pain, with a single study reporting medical side effects including syncope, dizziness, headache, gastritis, and tachycardia (17/1055 total patients).
LP-PRP results in improved functional outcome scores compared with hyaluronic acid and placebo when used for treatment of knee osteoarthritis. LP-PRP and LR-PRP have similar safety profiles, although both induce more transient reactions than does hyaluronic acid. Adverse reactions to PRP may not be directly related to leukocyte concentration.
© 2015 The Author(s).
Introduction:
We investigated the use of autologous bone marrow concentrate (BMC) with and without an adipose graft, for treatment of knee osteoarthritis (OA).
Methods:
Treatment registry data for patients who underwent BMC procedures with and without an adipose graft were analyzed. Pre- and posttreatment outcomes of interest included the lower extremity functional scale (LEFS), the numerical pain scale (NPS), and a subjective percentage improvement rating. Multivariate analyses were performed to examine the effects of treatment type adjusting for potential confounding factors. The frequency and type of adverse events (AE) were also examined.
Results:
840 procedures were performed, 616 without and 224 with adipose graft. The mean LEFS score increased by 7.9 and 9.8 in the two groups (out of 80), respectively, and the mean NPS score decreased from 4 to 2.6 and from 4.3 to 3 in the two groups, respectively. AE rates were 6% and 8.9% in the two groups, respectively. Although pre- and posttreatment improvements were statistically significant, the differences between the groups were not.
Conclusion:
BMC injections for knee OA showed encouraging outcomes and a low rate of AEs. Addition of an adipose graft to the BMC did not provide a detectible benefit over BMC alone.
Background:
The effect of platelet-rich plasma (PRP) on chondrocytes has been studied in cell and tissue culture, but considerably less attention has been given to the effect of PRP on synoviocytes. Fibroblast-like synoviocytes (FLS) compose 80% of the normal human synovium and produce cytokines and matrix metalloproteinases that can mediate cartilage catabolism.
Purpose:
To compare the effects of leukocyte-rich PRP (LR-PRP), leukocyte-poor PRP (LP-PRP), red blood cell (RBC) concentrate, and platelet-poor plasma (PPP) on human FLS to determine whether leukocyte and erythrocyte concentrations of PRP formulations differentially affect the production of inflammatory mediators.
Study design:
Controlled laboratory study.
Methods:
Peripheral blood was obtained from 4 donors and processed to create LR-PRP, LP-PRP, RBCs, and PPP. Human synoviocytes were cultured for 96 hours with the respective experimental conditions using standard laboratory conditions. Cell viability and inflammatory mediator production were then evaluated.
Results:
Treatment with LR-PRP resulted in significantly greater synoviocyte death (4.9% ± 3.1%) compared with LP-PRP (0.72% ± 0.70%; P = .035), phosphate-buffered saline (PBS) (0.39% ± 0.27%; P = .018), and PPP (0.26% ± 0.30%; P = .013). Synoviocytes treated with RBC concentrate demonstrated significantly greater cell death (12.5% ± 6.9%) compared with PBS (P < .001), PPP (P < .001), LP-PRP (P < .001), and LR-PRP (4.9% ± 3.1%; P < .001). Interleukin (IL)-1β content was significantly higher in cultures treated with LR-PRP (1.53 ± 0.86 pg/mL) compared with those treated with PBS (0.22 ± 0.295 pg/mL; P < .001), PPP (0.11 ± 0.179 pg/mL; P < .001), and RBCs (0.64 ± 0.58 pg/mL; P = .001). IL-6 content was also higher with LR-PRP (32,097.82 ± 22,844.300 pg/mL) treatment in all other groups (P < .001). Tumor necrosis factor-α levels were greatest in LP-PRP (9.97 ± 3.110 pg/mL), and this was significantly greater compared with all other culture conditions (P < .001). Interferon-γ levels were greatest in RBCs (64.34 ± 22.987 pg/mL) and significantly greater than all other culture conditions (P < .001).
Conclusion:
Treatment of synovial cells with LR-PRP and RBCs resulted in significant cell death and proinflammatory mediator production.
Clinical relevance:
Clinicians should consider using leukocyte-poor, RBC-free formulations of PRP when administering intra-articularly.
Micronized dehydrated human amnion/chorion membrane (mu-dHACM) is derived from donated human placentae and has anti-inflammatory, low immunogenic and anti-fibrotic properties. The objective of this study was to quantitatively assess the efficacy of mu-dHACM as a disease modifying intervention in a rat model of osteoarthritis (OA). It was hypothesized that intra-articular injection of mu-dHACM would attenuate OA progression.
Lewis rats underwent medial meniscal transection (MMT) surgery to induce OA. 24 hours post-surgery, mu-dHACM or saline was injected intra-articularly into the rat joint. Naive rats also received mu-dHACM injections. Microstructural changes in the tibial articular cartilage were assessed using equilibrium partitioning of an ionic contrast agent (EPIC-muCT) at 21 days post-surgery. The joint was also evaluated histologically and synovial fluid was analyzed for inflammatory markers at 3 and 21 days post-surgery.
There was no measured baseline effect of mu-dHACM on cartilage in naive animals. Histological staining of treated joints showed presence of mu-dHACM in the synovium along with local hypercellularity at 3 and 21 days post-surgery. In MMT animals, development of cartilage lesions at 21 days was prevented and number of partial erosions was significantly reduced by treatment with mu-dHACM. EPIC-muCT analysis quantitatively showed that mu-dHACM reduced proteoglycan loss in MMT animals.
mu-dHACM is rapidly sequestered in the synovial membrane following intra-articular injection and attenuates cartilage degradation in a rat OA model. These data suggest that intra-articular delivery of mu-dHACM may have a therapeutic effect on OA development.
Mesenchymal stem cells (MSCs) are partially defined by their ability to differentiate into tissues including bone, cartilage and adipose in vitro, but it is their trophic, paracrine and immunomodulatory functions that may have the greatest therapeutic impact in vivo. Unlike pharmaceutical treatments that deliver a single agent at a specific dose, MSCs are site regulated and secrete bioactive factors and signals at variable concentrations in response to local microenvironmental cues. Significant progress has been made in understanding the biochemical and metabolic mechanisms and feedback associated with MSC response. The anti-inflammatory and immunomodulatory capacity of MSC may be paramount in the restoration of localized or systemic conditions for normal healing and tissue regeneration. Allogeneic MSC treatments, categorized as a drug by regulatory agencies, have been widely pursued, but new studies demonstrate the efficacy of autologous MSC therapies, even for individuals affected by a disease state. Safety and regulatory concerns surrounding allogeneic cell preparations make autologous and minimally manipulated cell therapies an attractive option for many regenerative, anti-inflammatory and autoimmune applications.
We conducted a systematic review and meta-analysis of randomized saline-controlled trials to determine the safety and efficacy of US-approved intra-articular hyaluronic acid (IAHA) injections for symptomatic knee osteoarthritis. A total of 29 studies representing 4,866 unique subjects (IAHA: 2,673, saline: 2,193) were included. IAHA injection resulted in very large treatment effects between 4 and 26 weeks for knee pain and function compared to pre-injection values, with standardized mean difference (SMD) values ranging from 1.07-1.37 (all P < 0.001). Compared to saline controls, SMDs with IAHA ranged from 0.38-0.43 for knee pain and 0.32-0.34 for knee function (all P < 0.001). There were no statistically significant differences between IAHA and saline controls for any safety outcome, including serious adverse events (SAEs) (P = 0.12), treatment-related SAEs (P = 1.0), study withdrawal (P = 1.0), and AE-related study withdrawal (P = 0.46). We conclude that intra-articular injection of US-approved HA products is safe and efficacious in patients with symptomatic knee osteoarthritis.
In the present study, we describe six patients who received autologous mesenchymal stem cell (MSC) therapy for symptomatic carpometacarpal (CMC) joint and hand osteoarthritis (OA). Six patients who received injections of adult autologous culture expanded MSCs in their thumb CMC joints were followed for 1 year posttreatment, and matched with four procedure candidates who remained untreated. We observed positive outcomes in the treatment group for both symptoms and function related to the OA, compared with a reported worsening among the untreated controls. While these results should be interpreted with caution because of the small number of treated subjects and lack of placebo control and randomization, we find sufficient evidence for further investigation of MSC therapy as an alternative to more invasive surgery in patients with OA of the hand.
Specialized treatment of plantar fasciitis that can reduce inflammation and promote healing may be a possible alternative prior to surgical intervention. We report the results of a randomized clinical trial examining the efficacy of micronized dehydrated human amniotic/chorionic membrane (mDHACM) injection as a treatment for chronic refractory plantar fasciitis.
An institutional review board-approved, prospective, randomized, single-center clinical trial was performed. Forty-five patients were randomized to receive injection of 2 cc 0.5% Marcaine plain, then either 1.25 cc saline (controls), 0.5 cc mDHACM, or 1.25 cc mDHACM. Follow-up visits occurred over 8 weeks to measure function, pain, and functional health and well-being.
Significant improvement in plantar fasciitis symptoms was observed in patients receiving 0.5 cc or 1.25 cc mDHACM versus controls within 1 week of treatment and throughout the study period. At 1 week, American Orthopaedic Foot and Ankle Society (AOFAS) Hindfoot scores increased by a mean of 2.2 ± 17.4 points for controls versus 38.7 ± 11.4 points for those receiving 0.5 cc mDHACM (P < .001) and 33.7 ± 14.0 points for those receiving 1.25 cc mDHACM (P < .001). By week 8 AOFAS Hindfoot scores increased by a mean of 12.9 ± 16.9 points for controls versus 51.6 ± 10.1 and 53.3 ± 9.4 for those receiving 0.5 cc and 1.25 cc mDHACM, respectively (both P < .001). No significant difference in treatment response was observed in patients receiving 0.5 cc versus 1.25 cc mDHACM.
In patients with refractory plantar fasciitis, mDHACM is a viable treatment option. Larger studies are needed to confirm our findings.
Level I, prospective randomized study.
Background:
Specific growth factors have been proposed as therapeutic proteins for cartilage repair.
Hypothesis:
Platelet-rich plasma (PRP) provides symptomatic relief in early osteoarthritis (OA) of the knee.
Study design:
Randomized controlled trial; Level of evidence, 1.
Methods:
A total of 78 patients (156 knees) with bilateral OA were divided randomly into 3 groups. Group A (52 knees) received a single injection of PRP, group B (50 knees) received 2 injections of PRP 3 weeks apart, and group C (46 knees) received a single injection of normal saline. White blood cell (WBC)-filtered PRP with a platelet count 3 times that of baseline (PRP type 4B) was administered in all. All the groups were homogeneous and comparable in baseline characteristics. Clinical outcome was evaluated using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire before treatment and at 6 weeks, 3 months, and 6 months after treatment. They were also evaluated for pain by a visual analog scale, and overall satisfaction with the procedure and complications were noted.
Results:
Statistically significant improvement in all WOMAC parameters was noted in groups A and B within 2 to 3 weeks and lasting until the final follow-up at 6 months, with slight worsening at the 6-month follow-up. The mean WOMAC scores (pain, stiffness, physical function, and total score) for group A at baseline were 10.18, 3.12, 36.56, and 49.86, respectively, and at final follow-up were 5.00, 2.10, 20.08, and 27.18, respectively, showing significant improvement. Similar improvement was noted in group B (mean WOMAC scores at baseline: 10.62, 3.50, 39.10, and 53.20, respectively; mean WOMAC scores at final follow-up: 6.18, 1.88, 22.40, and 30.48, respectively). In group C, the mean WOMAC scores deteriorated from baseline (9.04, 2.70, 33.80, and 45.54, respectively) to final follow-up (10.87, 2.76, 39.46, and 53.09, respectively). The 3 groups were compared with each other, and no improvement was noted in group C as compared with groups A and B (P < .001). There was no difference between groups A and B, and there was no influence of age, sex, weight, or body mass index on the outcome. Knees with Ahlback grade 1 fared better than those with grade 2. Mild complications such as nausea and dizziness, which were of short duration, were observed in 6 patients (22.2%) in group A and 11 patients (44%) in group B.
Conclusion:
A single dose of WBC-filtered PRP in concentrations of 10 times the normal amount is as effective as 2 injections to alleviate symptoms in early knee OA. The results, however, deteriorate after 6 months. Both groups treated with PRP had better results than did the group injected with saline only.
Objective
To compare the effects of platelet-rich plasma injection with those of dry needling on shoulder pain and function in patients with rotator cuff disease.
Design
A single-centre, prospective, randomized, double-blinded, controlled study.
Setting
University rehabilitation hospital.
Participants
Thirty-nine patients with a supraspinatus tendon lesion (tendinosis or a partial tear less than 1.0 cm, but not a complete tear) who met the inclusion criteria recruited between June 2010 and February 2011.
Intervention
Two dry needling procedures in the control group and two platelet-rich plasma injections in the experimental group were applied to the affected shoulder at four-week intervals using ultrasound guidance.
Measurements
The Shoulder Pain and Disability Index, passive range of motion of the shoulder, a physician global rating scale at the six-month follow-up, adverse effects monitoring and an ultrasound measurement were used as outcome measures.
Results
The clinical effect of the platelet-rich plasma injection was superior to the dry needling from six weeks to six months after initial injection (P < 0.05). At six months the mean Shoulder Pain and Disability Index was 17.7 ± 3.7 in the platelet-rich plasma group versus 29.5 ± 3.8 in the dry needling group (P < 0.05). No severe adverse effects were observed in either group.
Conclusions
Autologous platelet-rich plasma injections lead to a progressive reduction in the pain and disability when compared to dry needling. This benefit is certainly still present at six months after treatment. These findings suggest that treatment with platelet-rich plasma injections is safe and useful for rotator cuff disease.
Adipose tissue-derived stem cells (ASCs) are considered as an attractive stem cell source for tissue engineering and regenerative medicine. We compared human bone marrow-derived mesenchymal stem cells (hMSCs) and hASCs under dynamic hydraulic compression to evaluate and compare osteogenic abilities. A novel micro cell chip integrated with microvalves and microscale cell culture chambers separated from an air-pressure chamber was developed using microfabrication technology. The microscale chip enables the culture of two types of stem cells concurrently, where each is loaded into cell culture chambers and dynamic compressive stimulation is applied to the cells uniformly. Dynamic hydraulic compression (1 Hz, 1 psi) increased the production of osteogenic matrix components (bone sialoprotein, oateopontin, type I collagen) and integrin (CD11b and CD31) expression from both stem cell sources. Alkaline phosphatase and Alrizarin red staining were evident in the stimulated hMSCs, while the stimulated hASCs did not show significant increases in staining under the same stimulation conditions. Upon application of mechanical stimulus to the two types of stem cells, integrin (β1) and osteogenic gene markers were upregulated from both cell types. In conclusion, stimulated hMSCs and hASCs showed increased osteogenic gene expression compared to non-stimulated groups. The hMSCs were more sensitive to mechanical stimulation and more effective towards osteogenic differentiation than the hASCs under these modes of mechanical stimulation.
In Europe and the United States, there is an increasing prevalence of the use of autologous blood products to facilitate healing in a variety of applications. Recently, we have learned more about specific growth factors, which play a crucial role in the healing process. With that knowledge there is abundant enthusiasm in the application of concentrated platelets, which release a supra-maximal quantity of these growth factors to stimulate recovery in non-healing injuries. For 20 years, the application of autologous PRP has been safely used and documented in many fields including; orthopedics, sports medicine, dentistry, ENT, neurosurgery, ophthalmology, urology, wound healing, cosmetic, cardiothoracic, and maxillofacial surgery. This article introduces the reader to PRP therapy and reviews the current literature on this emerging treatment modality. In summary, PRP provides a promising alternative to surgery by promoting safe and natural healing. However, there are few controlled trials, and mostly anecdotal or case reports. Additionally the sample sizes are frequently small, limiting the generalization of the findings. Recently, there is emerging literature on the beneficial effects of PRP for chronic non-healing tendon injuries including lateral epicondylitis and plantar fasciitis and cartilage degeneration (Mishra and Pavelko, The American Journal of Sports Medicine 10(10):1-5, 2006; Barrett and Erredge, Podiatry Today 17:37-42, 2004). However, as clinical use increases, more controlled studies are needed to further understand this treatment.
We have developed a new system for the production of autologous platelet-rich plasma and red blood cell concentrates to be used in autologous transfusion support of cardiac surgery patients. In 15 operations no homologous blood products were required. Costs were diminished since with the same harness it was possible to carry out the intraoperative blood salvage and concentrate the erythrocytes contained in the oxygenator and its lines. Indirect costs were also reduced since no infective complication was observed due to homologous blood products.
Future cell-based therapies such as tissue engineering will benefit from a source of autologous pluripotent stem cells. For mesodermal tissue engineering, one such source of cells is the bone marrow stroma. The bone marrow compartment contains several cell populations, including mesenchymal stem cells (MSCs) that are capable of differentiating into adipogenic, osteogenic, chondrogenic, and myogenic cells. However, autologous bone marrow procurement has potential limitations. An alternate source of autologous adult stem cells that is obtainable in large quantities, under local anesthesia, with minimal discomfort would be advantageous. In this study, we determined if a population of stem cells could be isolated from human adipose tissue. Human adipose tissue, obtained by suction-assisted lipectomy (i.e., liposuction), was processed to obtain a fibroblast-like population of cells or a processed lipoaspirate (PLA). These PLA cells can be maintained in vitro for extended periods with stable population doubling and low levels of senescence. Immunofluorescence and flow cytometry show that the majority of PLA cells are of mesodermal or mesenchymal origin with low levels of contaminating pericytes, endothelial cells, and smooth muscle cells. Finally, PLA cells differentiate in vitro into adipogenic, chondrogenic, myogenic, and osteogenic cells in the presence of lineage-specific induction factors. In conclusion, the data support the hypothesis that a human lipoaspirate contains multipotent cells and may represent an alternative stem cell source to bone marrow-derived MSCs.
This book provides an introductory overview of advancements in platelet-rich plasma (PRP), focusing on current technologies and methods, new challenges and controversies, and avenues for further research. With many studies demonstrating a role for PRP in improving response to injury, this book aims to facilitate the application of this rapidly growing treatment option for trauma patients.
Platelet Rich Plasma in Musculoskeletal Practice is a highly informative and carefully presented book, providing scientific and clinical insight for specialists who utilize PRP in daily practice, and for readers who are seeking to learn more about this effective injury treatment.
Background:
Bone marrow aspirate concentrate (BMAC) is increasingly used as a regenerative therapy for musculoskeletal pathological conditions despite limited evidence-based support.
Hypothesis:
BMAC will prove feasible, safe, and efficacious for the treatment of pain due to mild to moderate degenerative joint disease of the knee.
Study design:
Randomized controlled trial; Level of evidence, 2.
Methods:
In this prospective, single-blind, placebo-controlled trial, 25 patients with bilateral knee pain from bilateral osteoarthritis were randomized to receive BMAC into one knee and saline placebo into the other. Fifty-two milliliters of bone marrow was aspirated from the iliac crests and concentrated in an automated centrifuge. The resulting BMAC was combined with platelet-poor plasma for an injection into the arthritic knee and was compared with a saline injection into the contralateral knee, thereby utilizing each patient as his or her own control. Safety outcomes, pain relief, and function as measured by Osteoarthritis Research Society International (OARSI) measures and the visual analog scale (VAS) score were tracked initially at 1 week, 3 months, and 6 months after the procedure.
Results:
There were no serious adverse events from the BMAC procedure. OARSI Intermittent and Constant Osteoarthritis Pain and VAS pain scores in both knees decreased significantly from baseline at 1 week, 3 months, and 6 months ( P ≤ .019 for all). Pain relief, although dramatic, did not differ significantly between treated knees ( P > .09 for all).
Conclusion:
Early results show that BMAC is safe to use and is a reliable and viable cellular product. Study patients experienced a similar relief of pain in both BMAC- and saline-treated arthritic knees. Further study is required to determine the mechanisms of action, duration of efficacy, optimal frequency of treatments, and regenerative potential. Registration: ClinicalTrials.gov record 12-004459.
Aim:
Evaluate intra-articular injection of bone marrow concentrate (BMC), followed by platelet-rich plasma (PRP) injection at 8 weeks follow-up in moderate/severe osteoarthritis.
Design:
Single center, retrospective Case Series (n = 125).
Methods:
Bone marrow was aspirated/concentrated using a standardized technique. Patients received a single intra-articular injection of BMC, with follow-up injection of PRP at 8 weeks.
Results:
Median absolute pain reduction in all joints was five points (71.4%) on visual analog scale. Median patient satisfaction was 9.0/10, while 91.7% indicated that they would repeat the procedure and 94% said that they would recommend the procedure to a friend.
Conclusion:
Intra-articular injection of BMC, followed by a PRP injection, can provide short-term benefits in moderate-to-severe osteoarthritis.
1.1 Background: Epicondylitis is the second most frequently encountered head and upper limb musculoskeletal diagnosis in primary care clinics, with an incidence rate as high as 7/1,000 patients per year. Chronic or recalcitrant epicondylitis- more appropriately termed epicondylosis or elbow tendinosis- is not uncommon and represents a notable set of pathologies which account for lost recreation time, decreased quality of life, and workers compensation claims. A novel non-operative option has recently become available in the form of micronized dehydrated human amniotic/chorionic membrane (mDHACM) allograft. 1.2 Hypothesis: mDHACM allograft is known to be rich in anti-inflammatory cytokines and tissue inhibitors of metalloproteinase and IL-10. It also contains an abundance of growth factors and cytokines. In vivo and in vitro studies have shown reduction in scar tissue. We hypothesize that mDHACM allograft will be a viable treatment option in patients with epicondylosis. 1.3 Study design: Retrospective case series 1.4 Level of evidence: IV 1.5 Methods: Charts were retrospectively reviewed for 10 patients who received mDHACM allograft injections for treatment of medial or lateral epicondylosis.
Background:
Few nonoperative treatment options for knee osteoarthritis (OA) are available, but there is ongoing debate about the effectiveness of intra-articular (IA) hyaluronic acid (HA) injections. We investigated whether the formulation of IA HA, or its combined use with IA corticosteroid (CS), may be contributing to some of the reported variation in clinical outcomes.
Methods:
The 5% Part B Medicare data (2005-2012) were used to identify knee OA patients who underwent knee arthroplasty (KA). The time from diagnosis of OA to KA was compared between patients with (HA) and without (no HA) IA HA use, using quantile regression with propensity score adjustment. These were further stratified by type of IA HA. Patient factors associated with time to KA were also assessed using Cox regression.
Results:
The "HA" cohort was associated with a longer time to KA of 8.7 months (95% confidence interval: 8.3-9.1 months; P < .001) compared with the "no HA" cohort, with extended time to KA in the bioengineered Euflexxa IA HA cohort. Patient factors associated with longer time to KA included women, younger patients, minority patients, patients with fewer comorbidities, and IA CS injection use. Patients with both IA HA and IA CS had an additional 6.3 months (95% confidence interval: 5.5-7.0 months; P < .001) to KA over those with only IA HA.
Conclusion:
In a large cohort of elderly patients undergoing KA, there was a significant longer time from diagnosis of OA to KA in those receiving IA HA. It is unclear if the extended time may lead to less KA utilization.
Background: Although accepted as a conservative treatment option for knee osteoarthritis, the debate about the effectiveness of intra-articular treatment with hyaluronic acid (HA) is still ongoing because of contrasting outcomes in different clinical studies. Several well designed clinical studies showed a significant improvement in pain at follow-up compared with baseline but no significant improvement comparing the efficacy of HA with placebo (saline) or with other conservative treatment options. Notwithstanding the effectiveness of different types of intra-articular HA products, the question of whether one HA product is better than another is still unanswered. In this systematic review we compare the effects of intra-articularly administered HA with intra-articularly administered placebo in general and, more specifically, the effects of individual HA products with placebo. We also compare the efficacy of different HA products.
Methods: A systematic review of randomized controlled trials (RCTs) was conducted using databases including MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Clinical Trial Register and EMBASE.
Results: Seventy-four RCTs were included in this systematic review. HA improves pain by approximately 40–50% compared with baseline levels. However, when compared with saline the difference in efficacy is not that large. Due to a large ‘placebo effect’ of saline (approximately 30% pain reduction, persisting for at least 3 months) we determined a weighted mean difference between the efficacy of HA and saline of just 10.20 using the visual analog scale for pain. It is debatable whether this difference reaches the minimum clinically important difference. Comparing the different HA products, which vary in the molecular weight, concentration, and volume of HA, we were not able to conclude that one brand has a better efficacy than another due to the heterogeneity of the studies and outcomes.
Discussion: In the future it will be important to determine the exact mechanism of action of placebo as this may give us an idea of how to treat osteoarthritis more efficiently. Due to the limitations of this review (follow-up of just 3 months and large heterogeneity of the included studies), it is also important to compare the different HA products to determine which product(s), or which molecular weight range, concentration, or volume of HA is the best option to treat osteoarthritis. Our recommendation is to start large (multicenter) RCTs to give us more evidence about the efficacy of the different HA products.
Autologous cell therapies including platelet-rich plasma (PRP) and bone marrow concentrate (BMC) are increasingly popular options for soft tissue and joint-related diseases. Despite increased clinical application, conflicting research has been published regarding the efficacy of PRP, and few clinical publications pertaining to BMC are available. Preparations of PRP (and BMC) can vary in many areas, including platelet concentration, number of white blood cells, presence or absence of red blood cells, and activation status of the preparation. The potential effect of PRP characteristics on PRP efficacy is often not well understood by the treating clinician, and PRP characteristics, as well as the volume of PRP delivered, are unfortunately not included in the methods of many published research articles. It is essential to establish a standard reporting system for PRP that facilitates communication and the interpretation and synthesis of scientific investigations. Herein, the authors propose a new PRP classification system reflecting important PRP characteristics based on contemporary literature and recommend adoption of minimal standards for PRP reporting in scientific investigations. Widespread adoption of these recommendations will facilitate interpretation and comparison of clinical studies and promote scientifically based progress in the field of regenerative medicine.
Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.
To develop concise, up-to-date, patient-focused, evidence-based, expert consensus guidelines for the management of knee osteoarthritis, intended to inform patients, physicians, and allied health care professionals worldwide.
Thirteen experts from relevant medical disciplines (primary care, rheumatology, orthopedics, physical therapy, physical medicine and rehabilitation, and evidence-based medicine), three continents and ten countries (USA, UK, France, Netherlands, Belgium, Sweden, Denmark, Australia, Japan, and Canada) and a patient representative comprised the Osteoarthritis Guidelines Development Group (OAGDG). Based on previous OA guidelines and a systematic review of the osteoarthritis (OA) literature, twenty-nine treatment modalities were considered for recommendation. Evidence published subsequent to the 2010 OARSI guidelines was based on a systematic review conducted by the OARSI evidence team at Tufts Medical Center, Boston, USA. Medline, EMBASE, Google Scholar, Web of Science, and the Cochrane Central Register of Controlled Trials were initially searched in first quarter 2012 and last searched in March 2013. Included evidence was assessed for quality using AMSTAR criteria, and published criticism of included evidence was also considered. To provide recommendations for individuals with a range of health profiles and OA burden, treatment recommendations were stratified into four clinical subphenotypes. Consensus recommendations were produced using the Rand/UCLA Appropriateness method and Delphi voting process. Treatments were recommended as Appropriate, Uncertain, or Not Appropriate, for each of four clinical subphenotypes and accompanied by 1-10 risk and benefit scores.
Appropriate treatment modalities for all individuals with knee OA included biomechanical interventions, intra-articular corticosteroids, exercise (land-based and water-based), self-management and education, strength training, and weight management. Treatments appropriate for specific clinical subphenotypes included acetaminophen (paracetamol), balneotherapy, capsaicin, cane (walking stick), duloxetine, oral NSAIDs (COX-2 selective and non-selective), and topical NSAIDs. Treatments of uncertain appropriateness for specific clinical subphenotypes included acupuncture, avocado soybean unsaponfiables, chondroitin, crutches, diacerein, glucosamine, intra-articular hyaluronic acid, opioids (oral and transdermal), rosehip, transcutaneous electrical nerve stimulation, and ultrasound. Treatments voted not appropriate included risedronate and electrotherapy (neuromuscular electrical stimulation).
These evidence-based consensus recommendations provide guidance to patients and practitioners on treatments applicable to all individuals with knee OA, as well as therapies that can be considered according to individualized patient needs and preferences.
To assess the relative efficacy of intra-articular hyaluronic acid (IAHA) in comparison with non-steroidal anti-inflammatory drugs (NSAIDs) for knee osteoarthritis (OA).
We searched Medline, EMBASE, Google Scholar, ISI Web of Science, and Cochrane Database from inception until February 2013. Randomized controlled trials comparing HA with NSAIDs for knee OA were included if they reported at least one pain outcome. Two reviewers abstracted data and determined quality. Outcomes included pain, function, and stiffness. Random-effects meta-analyses were performed.
Five trials (712 participants) contributed to the pain analysis. Both groups showed improvement from baseline. The analysis found an effect size (ES) of -0.07 (95% CI: -0.24 to 0.10) at trial end, favoring neither treatment. There were no statistically significant differences between the groups at 4 and 12 weeks in function [ES = -0.08 (95% CI: -0.39 to 0.23)] or stiffness [ES = 0.03 (95% CI: -0.27 to 0.34)] analyses based on two trials. Injection site pain was the most common adverse event reported in the HA group, and gastrointestinal adverse events were more common in the NSAIDs group.
This meta-analysis suggests that IAHA is not significantly different from continuous oral NSAIDs at 4 and 12 weeks. Our study detected no safety concerns; however, the included trials had only a short follow-up duration. Given the favorable safety profile of IAHA over NSAIDs, this result suggests that IAHA might be a viable alternative to NSAIDs for knee OA, especially for older patients at greater risk for systemic adverse events.
Younger adults, aged < 65 years, increasingly present to their physicians with advanced cartilage disease or post-traumatic osteoarthritis. A number of treatments exist for lessening patient pain and improving patient function. However, many patients are becoming aware of the potential of regenerative therapies and are now seeking solutions to the impaired biology underlying their conditions rather than addressing only their symptoms. Patients do not want to merely lessen their symptoms temporarily with a surgical procedure that replaces damaged tissue, but instead seek correction and repair of the underlying biology to regenerate damaged tissue and alleviate their symptoms altogether. Current therapies for patients with cartilage disease or osteoarthritis range from non-surgical intra-articular injections with biologics, such as hyaluronic acid (HA), to total joint arthroplasty for advanced stages of disease. Total joint arthroplasty is a successful procedure for patients aged > 65 years; however, the limited long-term durability of implanted prostheses decreases the preference of using such methods in more active patients aged < 65 years. The potential of cell-based orthobiologic injection therapies (pertaining to therapeutic injectables that aim to restore the biologic environment and/or structural components of diseased or damaged musculoskeletal tissue) is of tremendous interest for younger, more active patients, and is even more appealing in that such therapy can be delivered at point-of-care in the clinic during an office visit. Notably, the exponential rate of progress in biotechnology has allowed for immediate application of myriad novel therapies prior to clear evidence of benefit from randomized clinical trials. Orthobiologic intra-articular injection therapies include HA and platelet-rich plasma (PRP). We report on current, available findings for a third-generation intra-articular orthobiologic injectable therapy for cartilage disease, bone marrow concentrate (BMC). Bone marrow concentrate contains mesenchymal stem cells (MSCs), hematopoetic stem cells, platelets (containing growth factors), and cytokines. The anti-inflammatory and immunomodulatory properties of bone marrow stem cells (BMSCs) can facilitate regeneration of tissue. Additionally, BMSCs enhance the quality of cartilage repair by increasing aggrecan content and tissue firmness. Following bone marrow aspiration (BMA), BMC is easily prepared using centrifugation, and is available for a same-day procedure with minimal manipulation of cells, thus complying with US Food and Drug Association (FDA) restrictions. To date, there are no published randomized controlled trials on the efficacy of use of autologous BMC intra-articular injections performed as a same-day in-office procedure for treating patients with cartilage disease; however, several publications have reported the ease of use of this method, its strong safety profile, and the fundamental science suggesting great therapeutic potential.
Background
Elbow tenderness and pain with resisted wrist extension are common manifestations of lateral epicondylar tendinopathy, also known as tennis elbow. Previous studies have suggested platelet-rich plasma (PRP) to be a safe and effective therapy for tennis elbow.
Purpose
To evaluate the clinical value of tendon needling with PRP in patients with chronic tennis elbow compared with an active control group.
Study Design
Randomized controlled trial; Level of evidence, 2.
Methods
A total of 230 patients with chronic lateral epicondylar tendinopathy were treated at 12 centers over 5 years. All patients had at least 3 months of symptoms and had failed conventional therapy. There were no differences in patients randomized to receive PRP (n = 116) or active controls (n = 114). The PRP was prepared from venous whole blood at the point of care and contained both concentrated platelets and leukocytes. After receiving a local anesthetic, all patients had their extensor tendons needled with or without PRP. Patients and investigators remained blinded to the treatment group throughout the study. A successful outcome was defined as 25% or greater improvement on the visual analog scale for pain.
Results
Patient outcomes were followed for up to 24 weeks. At 12 weeks (n = 192), the PRP-treated patients reported an improvement of 55.1% in their pain scores compared with 47.4% in the active control group ( P = .163). At 24 weeks (n = 119), the PRP-treated patients reported an improvement of 71.5% in their pain scores compared with 56.1% in the control group ( P = .019). The percentage of patients reporting significant elbow tenderness at 12 weeks was 37.4% in the PRP group versus 48.4% in the control group ( P = .143). Success rates for patients at 12 weeks were 75.2% in the PRP group versus 65.9% in the control group ( P = .104). At 24 weeks, 29.1% of the PRP-treated patients reported significant elbow tenderness versus 54.0% in the control group ( P = .009). Success rates for patients with 24 weeks of follow-up were 83.9% in the PRP group compared with 68.3% in the control group ( P = .037). No significant complications occurred in either group.
Conclusion
No significant differences were found at 12 weeks in this study. At 24 weeks, however, clinically meaningful improvements were found in patients treated with leukocyte-enriched PRP compared with an active control group.
To examine the effect of different sources of Good Manufacturing Practice clinical grade adipose-derived mesenchymal stem cells (AD-MSCs) on inflammatory factors in osteoarthritic (OA) chondrocytes and synoviocytes.
AD-MSCs from infrapatellar Hoffa fat, subcutaneous (SC) hip fat, and SC abdominal fat were cocultured in Transwells with chondrocytes or synoviocytes. Inflammatory factors (interleukin-1β [IL-1β], tumor necrosis factor α, IL-6, CXCL1/growth-related oncogene α, CXCL8/IL-8, CCL2/monocyte chemotactic protein 1, CCL3/macrophage inflammatory protein 1α, and CCL5/RANTES) were evaluated by quantitative reverse transcription-polymerase chain reaction or multiplex bead-based immunoassay. The role of different immunomodulators was analyzed.
All the inflammatory factors analyzed were down-modulated at the messenger RNA or protein level independently by all 3 AD-MSC sources or by allogeneic AD-MSCs used in coculture with chondrocytes or synoviocytes. Inflammatory factor down-modulation was observed only when AD-MSCs were cocultured with chondrocytes or synoviocytes that produced high levels of inflammatory factors, but no effect was observed in cells that produced low levels of those factors, thus highlighting a dependence of the AD-MSC effect on existing inflammation. The immunomodulators IL-10, IL-1 receptor antagonist, fibroblast growth factor 2, indoleamine 2,3-dioxygenase 1, and galectin 1 were not involved in AD-MSC effects, whereas the cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2 ) pathway exerted a role in the mechanism of antiinflammatory AD-MSC action.
The antiinflammatory effects of AD-MSCs are probably not dependent on AD-MSC adipose tissue sources and donors but rather on the inflammatory status of OA chondrocytes and synoviocytes. AD-MSCs seem to be able to sense and respond to the local environment. Even though a combination of different molecules may be involved in AD-MSC effects, the COX-2/PGE2 pathway may play a role, suggesting that AD-MSCs may be useful for therapies in osteoarticular diseases.
Ultrasound imaging has evolved as a very useful tool in medical science. However, the technique of ultrasound-guided bone marrow trephine biopsy (BMTB) has not been routinely used by haematologists and oncologists to help locate the posterior iliac crest during the BMTB procedure. We have used the technique of ultrasound-guided BMTB in 20 patients diagnosed with various haematological and non-haematological malignant conditions. We found the technique simple and useful in precisely locating the posterior iliac crest. As a result, it facilitates the extraction of a satisfactory core sample or aspiration biopsy and is more surgically precise than when access to the target bone is based only on external landmarks and blind biopsy.
To evaluate the therapeutic trajectory of intra-articular hyaluronic acid (IAHA) vs placebo for knee osteoarthritis (OA).
Our data sources include Medline, EMBASE, CINAHL, BIOSIS, Web of Science, Google Scholar, Cochrane database; hand searched reviews, manuscripts, and, supplements; author contacts for unpublished data. Randomized trials that reported effects of IAHA vs placebo on knee OA were selected based on inclusion criteria. We computed effect sizes for change from baseline at 4, 8, 12, 16, 20 and 24 weeks, using Bayesian random effects model. We performed multivariate analyses adjusting for correlation between time points. Meta-regressions were performed adjusting for potential confounders.
The 54 eligible trials included 7545 participants. The conduct and quality of these trials varied in number of aspects. The effect size (ES) favored IAHA by week 4 (0.31; 95% CI 0.17, 0.45), reaching peak at week 8 (0.46; 0.28, 0.65), and then trending downwards, with a residual detectable effect at week 24 (0.21; 0.10, 0.31). This therapeutic trajectory was consistent among the subset of high quality trials and on multivariate analysis adjusting for correlation between time points.
Our meta-analysis highlights a therapeutic trajectory of IAHA for knee OA pain over 6 months post-intervention. With this additional perspective, we are able to infer that IAHA is efficacious by 4 weeks, reaches its peak effectiveness at 8 weeks and exerts a residual detectable at 24 weeks. On the other hand, the peak effect size (0.46; 0.28, 0.65), is greater than published effects from other OA analgesics [acetaminophen (ES=0.13; 0.04, 0.22); NSAIDs (ES=0.29; 0.22, 0.35); COX-2 inhibitors (ES=0.44; 0.33, 0.55)]. An effect size above 0.20 is considered to be clinically relevant on an individual patient basis in chronic pain conditions such as knee OA. Thus, its properties could have utility for certain clinical situations, or in combination with other therapies.
The human amniotic membrane (HAM) is a highly abundant and readily available tissue. This amniotic tissue has considerable advantageous characteristics to be considered as an attractive material in the field of regenerative medicine. It has low immunogenicity, anti-inflammatory properties and their cells can be isolated without the sacrifice of human embryos. Since it is discarded post-partum it may be useful for regenerative medicine and cell therapy. Amniotic membranes have already been used extensively as biologic dressings in ophthalmic, abdominal and plastic surgery. HAM contains two cell types, from different embryological origins, which display some characteristic properties of stem cells. Human amnion epithelial cells (hAECs) are derived from the embryonic ectoderm, while human amnion mesenchymal stromal cells (hAMSCs) are derived from the embryonic mesoderm. Both populations have similar immunophenotype and multipotential for in vitro differentiation into the major mesodermal lineages, however they differ in cell yield. Therefore, HAM has been proposed as a good candidate to be used in cell therapy or regenerative medicine to treat damaged or diseased tissues.
Mesenchymal stem cells (MSCs) are multi-potent adult stem cells harboring multi-lineage differentiation potential and immunosuppressive properties that make MSCs an ideal candidate cell type for immunomodulation and regenerative medicine. Currently, MSC-related researches and clinical trials have evoked exciting promise in a variety of disorders and tissue regeneration. However, it must be recognized that several critical potential problems have also emerged from current clinical trials, for example: (1) the indefinite association between the phenotypic characteristics and the biological functions of MSCs; (2) the lack of clinical data to support the long-term safety of MSCs; (3) the need for further clarification of multiple mechanisms of MSC transplant actions in vivo; and (4) the lack of comparability of MSC transplant efficacy. Therefore, MSC-based therapies could not yet be considered a routine treatment in the clinic. Based on these, we proposed that large-scale and multi-center clinical trials of MSC-based therapies should be initiated under strict supervision. These interventions might help to establish a new clinical paradigm to turn MSC transplantation into a routine therapy for at least some diseases in the near future.
To repair rabbit tendon defects with tissue engineering method.
The third passage of fetal skin fibroblast cells was labeled with 5-bromo-2' deoxyuridine (Brdu) and then seeded on human amnion extracellular matrix (HA-ECM). Using 1 cm-long-Achilles tendon defects as repairing models in the experimental group, tendon defects were core bridged with polydioxanone (PDS) and then capsulated with the complex of fibroblasts-HA-ECM. In the control group I, defective tendons were sutured with PDS following the former procedure and capsulated with HA-ECM (without fibroblasts). In the control group II, only PDS was applied to connect the defective tendons. Gross examination, light microscopy, scanning electronmicroscopy and biomechanical measurement of the repaired tendons were respectively performed at postoperative 1, 2, 3 month as well as immunohistochemical examination.
The optimal cell concentration for seeding fibroblasts was 3.5 x 10(6) cells/ml. Cells grew well and radiated or paralleled on HA-ECM. Immunohistochemistry showed that the labeled seed fibroblasts played an important role in tendonization. The results of light microscopy, electron microscopy, and biomechanical assessment suggested that the rate and quality of tendonization in the experimental group was superior to those of the control group I and II. The tensile strength in the experimental group was the greatest, the next was in the control group I, and the worst in the control group II (P<0.05).
HA-ECM is the excellent carrier for fibroblasts. Fibroblasts-HA-ECM complex has the capability to repair tendon defect and to tendonize with rapid rate and good performance three months after operation. Its tensile strength is 81.8% of that of normal tendon.
Multipotent stem cells constitute an unlimited source of differentiated cells that could be used in pharmacological studies and in medicine. Recently, several publications have reported that adipose tissue contains a population of cells able to differentiate into different cell types including adipocytes, osteoblasts, myoblasts, and chondroblasts. More recently, stem cells with a multi-lineage potential at the single cell level have been isolated from human adipose tissue. These cells, called human Multipotent Adipose-Derived Stem (hMADS) cells, have been established in culture and interestingly, maintain their characteristics with long-term passaging. The adipocyte differentiation of hMADS cells has been thoroughly studied and differentiated cells exhibit the unique feature of human adipocytes. Finally, potential applications of stem cells isolated from adipose tissue in medicine will be discussed.
Orthobiologics: A new frontier in orthopaedics
- S Sampson
- H Vincent
- D Aufiero
Hyaluronic acid in the treatment of knee osteoarthritis: a systematic review and meta-analysis with emphasis on the efficacy of different products
- S Colen
- Mp Van Den Bekerom
- M Mulier
- D Haverkamp
Multilineage cells from human adipose tissue: implications for cell-based therapies
- P A Zuk
- M Zhu
- H Mizuno
- J Huang
- J W Futrell
- A J Katz
- PA Zuk
Efficacy of platelet-rich plasma for chronic tennis elbow: a double-blind, prospective, multicenter, randomized controlled trial of 230 patients
- A K Mishra
- N V Skrepnik
- S G Edwards
- G L Jones
- S Sampson
- D A Vermillion
- AK Mishra