Cell Transplantation (CELL TRANSPLANT)

Publications in this journal

• Article: Environmental biomechanics substantiated by defined pillar micropatterns govern behavior of human mesenchymal stem cells.

  Proksch S, Steinberg T, Schulz S, Sauerbier S, Hellwig E, Tomakidi P
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  ABSTRACT: Objective: While evidence on the impact of the biomechanical environment elasticity on human mesenchymal stem cell (hMSC) behavior is growing, the aspect of micro-patterning is still poorly understood. Thus, the present study aimed at investigating the influence of defined environmental micropatterning on hMSC behavior.Material & Methods: Following characterization, hMSCs were grown on defined pillar micropatterns of 5, 7, 9 and 11 μm. With respect to cell behavior, primary hMSC adhesion was detected by indirect immunofluorescence (iIF) for paxillin, vinculin, integrin alphaV, and actin, while proliferation was visualized by histone H3. Morphogenesis was monitored by scanning electron microscopy and the expression of stem cell-specific biomarkers by realtime PCR.Results: Favouritism of primary adhesion of hMSCs on pillar tops occurred at smaller pillar micropatterns, concomitant with cell flattening. While vinculin, integrin alpha V and paxillin appeared initially more cytoplasmic, high pillar micropatterns favoured a progressive redistribution with polarization to cell tension sites and at cell borders. Accomplishment of morphogenesis at day 3 revealed establishment of fully rotund cell somata at 5 μm, whilehMSCs appeared progressively elongated at rising micropatterns. The hMSC proliferation capacity was influenced by pillar micropatterns and gene expression analysis of stem cell- and differentiation-associated biomarkers disclosed clear modulation by distinct pillarmicropatterns.Conclusion: In response to environmental biomechanics, our results show that hMSC behavior is governed by pillar micropatterning. In turn, these findings may form the basis to prospectively direct lineage specificity of hMSCs in a customized fashion.
  Cell Transplantation 04/2012;
• Article: Comparative Analysis of Telomere Length, Telomerase and Reverse Transcriptase Activity in Human Dental Stem Cells

  Byeong-Gyun Jeon, Eun-Ju Kang, B. Mohana Kumar, Geun-Ho Maeng, Sun-A Ock, Dae-Oh Kwack, Bong-Wook Park, Gyu-Jin Rho
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  ABSTRACT: Stem cells from dental tissues have been isolated and established for tooth regenerative applications. However, basic characterization on their biological properties still needs to be investigated before employing them for effective clinical trials. In this study, we compared the telomere length, relative telomerase activity (RTA), and relative reverse transcriptase activity (RRA) as well as the surface antigen profile and mesenchymal differentiation ability in human dental papilla stem cells (DPaSCs), dental pulp stem cells (DPuSCs), and dental follicle stem cells (DFSCs) with mesenchymal stem cells (MSCs) derived from bone marrow. Dental stem cells (DSCs) were strongly positive for cell surface markers, such as CD44 and CD90. However, slightly lower expression of CD105 was observed in DPaSCs and DPuSCs compared to DFSCs and MSCs. Following specific induction, DPaSCs, DFSCs, and MSCs were successfully differentiated into adipocytes and osteocytes. However, DPuSCS, in particular, were able to differentiate into adipocytes but failed to induce into osteogenic differentiation. Further, all DSCs, MSCs, and MRC-5 fibroblasts as control were investigated for telomere length by nonradioactive chemiluminescent assay, RTA by relative-quantitative telomerase repeat amplification protocol (RQ-TRAP), and RRA by PCR-based assay. Mean telomere lengths in DPaSCs, DPuSCs, DFSCs, and MSCs was ∼11 kb, and the values did not differ significantly (p < 0.05) among the cells analyzed. RTA levels in DPaSCs were significantly (p < 0.05) higher than in MSCs, DPuSCs, DFSCs, and MRC-5 fibroblasts and among DSCs, DFSCs showed a significantly (p < 0.05) lower RTA. Moreover, RRA levels were significantly (p < 0.05) higher in DPaSCs, DPuSCs, and MSCs than in DFSCs. Based on these observations, we conclude that among DSCs, DPaSCs possessed ideal characteristics on telomere length, telomerase activity and reverse transcriptase (RTase) activity, and may serve as suitable alternative candidates for regenerative medicine.
  Cell Transplantation 10/2011; 20(11-12):1693-1705.
• Article: Establishment, Characterization, and Successful Adaptive Therapy Against Human Tumors of NKG Cell, a New Human NK Cell Line

  Min Cheng, Juan Ma, Yongyan Chen, Jianhua Zhang, Weidong Zhao, Jian Zhang, Haiming Wei, Bin Ling, Rui Sun, Zhigang Tian
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  ABSTRACT: Natural killer (NK) cells play important roles in adoptive cellular immunotherapy against certain human cancers. This study aims to establish a new human NK cell line and to study its role for adoptive cancer immunotherapy. Peripheral blood samples were collected from 54 patients to establish the NK cell line. A new human NK cell line, termed as NKG, was established from a Chinese male patient with rapidly progressive non-Hodgkin's lymphoma. NKG cells showed LGL morphology and were phenotypically identified as CD56bright NK cell with CD16−, CD27−, CD3−, αβTCR−, γδTCR−, CD4−, CD8−, CD19−, CD161−, CD45+, CXCR4+, CCR7+, CXCR1−, and CX3CR1−. NKG cells showed high expression of adhesive molecules (CD2, CD58, CD11a, CD54, CD11b, CD11c), an array of activating receptors (NKp30, NKp44, NKp46, NKG2D, NKG2C), and cytolysis-related receptors and molecules (TRAIL, FasL, granzyme B, perforin, IFN-γ). The cytotoxicity of NKG cells against tumor cells was higher than that of the established NK cell lines NK-92, NKL, and YT. NKG cell cytotoxicity depended on the presence of NKG2D and NKp30. When irradiated with 8 Gy, NKG cells were still with high cytotoxicity and activity in vitro and with safety in vivo, but without proliferation. Further, the irradiated NKG cells exhibited strong cytotoxicity against human primary ovarian cancer cells in vitro, and against human ovarian cancer in a mouse xenograft model. The adoptive transfer of NKG cells significantly inhibited the ovarian tumor growth, decreased the mortality rate and prolonged the survival, even in cases of advanced diseases. A number of NKG cells were detected in the ovarian tumor tissues during cell therapy. In use of the new human NK cell line, NKG would a promising cellular candidate for adoptive immunotherapy of human cancer.
  Cell Transplantation 10/2011; 20(11-12):1731-1746.
• Article: Characterization of Human Umbilical Cord Lining-Derived Epithelial Cells and Transplantation Potential

  Yue Zhou, Shu Uin Gan, Gen Lin, Yan Ting Lim, Jeyakumar Masilamani, Fatimah Bte Mustafa, Meow Ling Phua, Laura Rivino, Toan Thang Phan, Kok Onn Lee, Roy Calne, Paul A. MacAry
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  ABSTRACT: In this study we describe the derivation and immunological characterization of a primary epithelial cell type from the human umbilical cord membrane. These cord lining epithelial cells (CLECs) expressed and/or secreted isoforms of the nonclassical human leukocyte antigen class I (HLA-1b) glycoproteins, HLA-G and E. Conditioned media from CLECs inhibited mitogen-stimulated T-lymphocyte responses, and in a mixed leukocyte reaction (MLR) assay, cocultured CLECs inhibited allogeneic responses with a concomitant reduction in proinflammatory cytokines. Using a transwell coculture system, it was demonstrated that these immunoregulatory effects were mediated by soluble factors secreted by CLECs, in a dose-dependent manner. Functional studies using HLA-G blocking antibody showed that the effects of CLEC-secreted products could be inhibited, thus demonstrating a significant and important role for soluble HLA-G. In vivo, we show that transplanted CLECs could be maintained for extended periods in immunocompetent mice where xenorejection rapidly destroyed primary keratinocytes, a control human epithelial cell type. Additionally, CLECs delayed the rejection of keratinocytes and extended their survival when cotransplanted, indicating an ability to protect adjacent human cell types that would otherwise be rejected if transplanted alone. We also show that CLECs transduced with a modified human proinsulin gene were transplanted intraperitoneally into streptozotocin (STZ)-induced diabetic mice, resulting in significantly lower levels of serum glucose compared to control mice. This study has characterized the immunological properties of CLECs and tested a potential therapeutic application in the treatment of a type 1 diabetes mouse model.
  Cell Transplantation 10/2011; 20(11-12):1827-1841.
• Article: Multitract Microtransplantation Increases the Yield of DARPP-32-Positive Embryonic Striatal Cells in a Rodent Model of Huntington's Disease

  Wei Jiang, Fabian Büchele, Anna Papazoglou, Máté Döbrössy, Guido Nikkhah
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  ABSTRACT: Embryonic striatal graft-mediated functional recovery in the rodent lesion model of Huntington's disease (HD) has been shown to correlate with the proportion of dopamine- and adenosine 3′,5′-monophosphate-regulated phosphoprotein with a molecular weight of 32 kDa (DARPP-32)-positive neurons in the graft. The current study investigated the impact of graft distribution on the yield of DARPP-32-positive cells in the grafts following either single-tract or multitract cell delivery protocols using the microtransplantation approach. Cells derived from the whole ganglionic eminence of E15 rat embryos, ubiquitously expressing green fluorescent protein (GFP), were implanted into unilaterally QA-lesioned rat striatum either as 2 × 1.8 μl macrodeposits in a single tract, or as 18 × 0.2 μl microdeposits disseminated over six needle, multitract, penetrations. For both groups, an ultrathin glass capillary with an outer diameter of 50 μm was used. Histological assessment at 4 months after transplantation showed nearly twofold increase of DARRP-32-positive striatal-like neurons in the multitract compared to the single-tract group. However, the cellular make-up of the grafts did not translate into functional differences as tested in a basic spontaneous behavior test. Furthermore, the volumetric values for overall volume, DARPP-32-positive patches, and dopaminergic projection zones were similar between both groups. The results show that distribution of fetal striatal tissue in multiple submicroliter deposits provides for an increased yield of striatal-like neurons, potentially due to the enlargement of the graft-host border area intensifying the graft's exposure to host-derived factors. Furthermore, the use of embryonic tissue from GFP donors was validated in cell-based therapy studies in the HD model.
  Cell Transplantation 09/2011; 20(10):1515-1527.
• Article: Efficient Derivation and Concise Gene Expression Profiling of Human Embryonic Stem Cell-Derived Mesenchymal Progenitors (EMPs)

  Men-Luh Yen, Chun-Han Hou, Kai-Yen Peng, Pei-Chi Tseng, Shih-Sheng Jiang, Chia-Tung Shun, Yao-Chang Chen, Min-Liang Kuo
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  ABSTRACT: New potential sources of stem cells for clinical application include bone marrow mesenchymal stem cells (BMMSCs), human embryonic stem cells (hESCs), and induced pluripotent stem cells (iPS). However, each source is not without its own concerns. While research continues in an effort to overcome these problems, the generation of mesenchymal progenitors from existing hESC lines may circumvent many of these issues. We report here a simple and efficient method of generating hESC-derived mesenchymal progenitors (EMPs) and transcriptome profiling using a concise, custom-designed, oligomnucleotide gene expression microarray. Characterization of EMPs shows that these cells are similar to BMMSCs in terms of differentiation capacity as well as cell surface marker expression. In addition, EMPs express several ESC markers and HLA-G, a nonclassical MHC class I molecule with immunomodulatory properties. Morevoer, EMPs possess significantly enhanced proliferative ability over BMMSCs during which karyotypic stability was maintained. Although derived from hESCs, EMPs do not form any tumors in immunocompromised mice. To efficiently profile gene expression in multiple samples, we designed an oligoarray to probe just over 11,000 genes highly expressed in stem cells. We found that the transcriptome of EMPs is more similar to BMMSCs than hESCs. Both cell types highly express genes involved in processes related to the cytoskeleton, extracellular matrix, and cell adhesion, but EMPs show higher expression of genes involved in cell proliferation whereas BMMSCs showed higher expression of immune-related genes. Based on our data, EMPs may be an accessible source of mesenchymal progenitor for therapeutic use.
  Cell Transplantation 09/2011; 20(10):1529-1545.
• Article: Technology and Innovation: 2010 a Year in Review

  Paul R. Sanberg, Cecilia Vindrola-Padros, David J. Eve, Howard J. Federoff
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  ABSTRACT: The following commentary provides a discussion of the articles published in Technology and Innovation in 2010 and where possible places them into context with those reported in Cell Transplantation. These articles can be divided into the following topics: a) models for innovation and technological commercialization, b) the ethical and legal consequences of the emergence of new technologies, c) research on novel technologies and methods, and d) the difficulties involved in peer review and scientific assessment. The articles shed light on the effects of technological innovation and commercialization on scientific ethical regulation, the establishment of legal standards for the protection of intellectual property, and the development of financial models.
  Cell Transplantation 07/2011; 20(8):1315-1319.
• Article: Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Protect Against Neuronal Cell Death and Ameliorate Motor Deficits in Niemann Pick Type C1 Mice

  Yoojin Seo, Se-Ran Yang, Min Ki Jee, Eun Kyung Joo, Kyung-Hwan Roh, Min-Soo Seo, Tae Hee Han, So Yeong Lee, Pan Dong Ryu, Ji-Won Jung, Kwang-Won Seo, Soo-Kyung Kang, Kyung-Sun Kang
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  ABSTRACT: Niemann Pick disease type C1 (NPC) is an autosomal recessive disease characterized by progressive neurological deterioration leading to premature death. In this study, we hypothesized that human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) have the multifunctional abilities to ameliorate NPC symptoms in the brain. To test this hypothesis, hUCB-MSCs were transplanted into the hippocampus of NPC mice in the early asymptomatic stage. This transplantation resulted in the recovery of motor function in the Rota Rod test and impaired cholesterol homeostasis leading to increased levels of cholesterol efflux-related genes such as LXRα, ABCA1, and ABCG5 while decreased levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase were observed in NPC mice. In the cerebrum, hUCB-MSCs enhanced neuronal cell survival and proliferation, where they directly differentiated into electrically active MAP2-positive neurons as demonstrated by whole-cell patch clamping. In addition, we observed that hUCB-MSCs reduced Purkinje neuronal loss by suppression of inflammatory and apoptotic signaling in the cerebellum as shown by immunohistochemistry. We further investigated how hUCB-MSCs enhance cellular survival and inhibit apoptosis in NPC mice. Neuronal cell survival was associated with increased PI3K/AKT and JAK2/STAT3 signaling; moreover, hUCB-MSCs modulated the levels of GABA/glutamate transporters such as GAT1, EAAT2, EAAT3, and GAD6 in NPC mice as assessed by Western blot analysis. Taken together, our findings suggest that hUCB-MSCs might play multifunctional roles in neuronal cell survival and ameliorating motor deficits of NPC mice.
  Cell Transplantation 06/2011; 20(7):1033-1047.
• Article: Bone Marrow Mononuclear Cells Increase Retinal Ganglion Cell Survival and Axon Regeneration in the Adult Rat

  Camila Zaverucha-do-Valle, Fernanda Gubert, Michelle Bargas-Rega, Juliana L. L. Coronel, Louise A. Mesentier-Louro, Andre Mencalha, Eliana Abdelhay, Marcelo F. Santiago, Rosalia Mendez-Otero
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  ABSTRACT: The central nervous system (CNS) of adult mammals generally does not regenerate, and many studies have attempted to identify factors that could increase neuroprotection and/or axonal outgrowth after CNS lesions. Using the optic nerve crush of rats as a model for CNS injury, we investigated the effect of intravitreal transplantation of syngeneic bone-marrow mononuclear cells (BMMCs) on the survival of retinal ganglion cells (RGC) and on the regeneration of optic axons. Control animals received intravitreal saline injections after lesion. Injections of BMMCs resulted in a 1.6-fold increase in the number of RGCs surviving 14 days after injury. The BMMC-treated animals also had increased numbers of axons, which grew up to 1.5 mm from the crush site, and also had reduced Müller glia activation. Analysis of mRNAs in all conditions revealed an increase in levels of fibroblast growth factor 2 (FGF-2) mRNA in treated animals 14 days after injury. To investigate whether the regenerated axons could reach the brain, we retrograde labeled the RGCs by injecting a lipophilic tracer into the superior colliculus. We also analyzed the expression of NGFI-A in the superficial layers of the superior colliculus as a possible marker of synaptic input from RGC axons. We found evidence that more RGCs were able to reach the brain after treatment and we showed that NGFI-A expression was higher in the treated animals 60 days after injury. These results demonstrate that transplant of BMMCs can increase neuroprotection and neuroregeneration after injury in a model of optic nerve crush, and these effects could be mediated by FGF-2.
  Cell Transplantation 02/2011; 20(3):391-406.
• Article: Bone Marrow Mononuclear Cells Increase Retinal Ganglion Cell Survival and Axon Regeneration in the Adult Rat

  Camila Zaverucha-do-Valle, Fernanda Gubert, Michelle Bargas-Rega, Juliana L. L. Coronel, Louise A. Mesentier-Louro, Andre Mencalha, Eliana Abdelhay, Marcelo F. Santiago, Rosalia Mendez-Otero
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  ABSTRACT: The central nervous system (CNS) of adult mammals generally does not regenerate, and many studies have attempted to identify factors that could increase neuroprotection and/or axonal outgrowth after CNS lesions. Using the optic nerve crush of rats as a model for CNS injury, we investigated the effect of intravitreal transplantation of syngeneic bone-marrow mononuclear cells (BMMCs) on the survival of retinal ganglion cells (RGC) and on the regeneration of optic axons. Control animals received intravitreal saline injections after lesion. Injections of BMMCs resulted in a 1.6-fold increase in the number of RGCs surviving 14 days after injury. The BMMC-treated animals also had increased numbers of axons, which grew up to 1.5 mm from the crush site, and also had reduced Müller glia activation. Analysis of mRNAs in all conditions revealed an increase in levels of fibroblast growth factor 2 (FGF-2) mRNA in treated animals 14 days after injury. To investigate whether the regenerated axons could reach the brain, we retrograde labeled the RGCs by injecting a lipophilic tracer into the superior colliculus. We also analyzed the expression of NGFI-A in the superficial layers of the superior colliculus as a possible marker of synaptic input from RGC axons. We found evidence that more RGCs were able to reach the brain after treatment and we showed that NGFI-A expression was higher in the treated animals 60 days after injury. These results demonstrate that transplant of BMMCs can increase neuroprotection and neuroregeneration after injury in a model of optic nerve crush, and these effects could be mediated by FGF-2.
  Cell Transplantation 02/2011; 20(3):391-406.
• Article: Book Review: Stem Cells and Myocardial Regeneration.

  Nelson Junior, Adriana Invitti, Eduardo Cruz, Enio Buffolo
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  ABSTRACT: [no abstract].
  Cell Transplantation 07/2009;
• Article: Cardiac Stem Cell Therapy: Advances From 2008.

  Amit Patel, Warren Sherman
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  ABSTRACT: Advances on multiple scientific fronts have brought insights into mechanisms of tissue healing and uncovered new potential to cellular recovery and replacement. With the unabated rise in the prevalence of cardiovascular disease, the interventional community is increasingly faced with caring for patients with chronic coronary, peripheral vascular, myocardial and conduction system diseases. The International Conference on Cell Therapy for Cardiovascular Diseases (IC3D) 2008 maintained its principal goal of integrating basic, translational and clinical data and manuscripts for this special issue of "Cell Transplantation" were submitted by its faculty. Several themes emerged from IC3D 2008. One in particular was the role played by tissue engineers in directing, and clarifying, important aspects of bedside-to-bench studies. The expertise of scientists in this multifaceted discipline may be crucial to the rapid conduct of hypothesis testing.
  Cell Transplantation 06/2009;
• Article: NF-kappaB Activity in Endothelial Cells is Modulated by Cell Substratum Interactions and Influences Chemokine-Mediated Adhesion of Natural Killer Cells.

  Shmuel Hess, Heiko Methe, Jong-Oh Kim, Elazer Edelman
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  ABSTRACT: BACKGROUND AND OBJECTIVES: As changes in sub-endothelial matrix composition are associated with alterations of the endothelial immune phenotype we sought to understand if cytokine-induced NF-kappaB activity and downstream effects depend on substrate adherence of endothelial cells (EC). METHODS: We compared the upstream phosphorylation cascade, activation of NF-kappaB, and expression/secretion of downstream effects of EC grown on tissue-culture polystyrene plates (TCPS) with EC embedded within collagen-based matrices (MEEC). Adhesion of natural killer (NK)-cells was quantified in vitro and in vivo. RESULTS: NF-kappaB subunit p65 nuclear levels were significantly lower and p50 significantly higher in cytokine stimulated MEEC than in EC-TCPS. Despite similar surface expression of TNF-alpha-receptors MEEC had significantly decreased secretion and expression of IL-6, IL-8, MCP-1, VCAM-1 and ICAM-1. Attenuated fractalkine expression and secretion in MEEC (2-3-fold lower than in EC-TCPS; p<0.0002) correlated with 3.7 fold lower NK-cell adhesion to EC (6335+/-420 vs. 1735+/-135 cpm; p<0.0002). Furthermore, NK-cell infiltration into sites of EC-implantation in vivo was significantly reduced when EC were embedded within matrix. CONCLUSIONS: Matrix embedding enables control of EC-substratum interaction. This in turn regulates chemokine and surface molecule expression and secretion, in particular of those compounds within NF-kappaB pathways, chemoattraction of NK-cells, local inflammation and tissue repair.
  Cell Transplantation 06/2009;
• Article: Percutaneous Cell Delivery into the Heart using Hydrogels Polymerizing in situ.

  Timothy Martens, Amandine Godier, Jonathan Parks, Leo Wan, Michael Koeckert, George Eng, Barry Hudson, Warren Sherman, Gordana Vunjak-Novakovic
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  ABSTRACT: Heart disease is the leading cause of death in the U.S. Following an acute myocardial infarction, a fibrous, noncontractile scar develops, and results in congestive heart failure in more than 500,000 patients in the U.S. each year. Muscle regeneration and the induction of new vascular growth to treat ischemic disorders of the heart can have significant therapeutic implications. Early studies in patients with chronic ischemic SLVD using skeletal myoblasts or bone marrow-derived cells report improvement in left ventricular ejection function (LVEF) and clinical status, without notable safety issues. Nonetheless, the efficacy of cell-transfer for cardiovascular disease is not established, in part due to a lack of control over cell retention, survival and function following their delivery. We studied the use of biocompatible hydrogels polymerizable in situ as a cell delivery vehicle, to improve cell retention, survival, and function following delivery into the ischemic myocardium. The study was conducted using human bone marrow derived mesenchymal stem cells and fibrin glue, but the methods are applicable to any human stem cells (adult or embryonic) and a wide range of hydrogels. We first evaluated the utility of several commercially available percutaneous catheters for delivery of viscous cell-hydrogel suspensions. Next we characterized the polymerization kinetics of fibrin glue solutions to define the ranges of concentrations compatible with catheter delivery. We then demonstrate the in vivo effectiveness of this preparation and its ability to increase cell retention and survival in a nude rat model of myocardial infarction.
  Cell Transplantation 06/2009;
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  Article: EARLY TRANSLATION OF ADIPOSE DERIVED CELL THERAPY FOR CARDIOVASCULAR DISEASE.

  Ricardo Sanz-Ruiz, Eugenia Fernández-Santos, Marta Domínguez-Muñoa, Radoslaw Parma, Adolfo Villa, Lucía Fernández, Pedro Sánchez, Francisco Fernández-Avilés
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  ABSTRACT: Over the past decade, cell therapy has emerged as a new approach to reversing myocardial ischemia. Several types of adult stem cells have been studied in both preclinical and clinical conditions for this purpose: bone marrow cells, circulating cells and myoblasts. Nevertheless, the quest for the ideal "anti-ischemic" cell is still ongoing. Recently, the existence of a population of stem cells located in adipose tissue (adipose-derived stem cells) has been observed. These are able to differentiate into multiple cell lineages including cardiomyocytic differentiation. In this review we discuss the basic principles of adipose-derived stem cells (types and characteristics, harvesting and expansion), the initial experimental studies and the currently ongoing clinical trials.
  Cell Transplantation 06/2009;
• Article: A simple breeding protocol for the procurement of accurately staged rat donor embryos for neural transplantation.

  U Weyrauch, E Torres, A Baird, S Dunnett
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  ABSTRACT: Obtaining accurately staged rat embryos can be difficult because of the variety of breeding protocols employed and because precise staging cannot be confirmed until excision of the embryos from the dam. The detection of oestrus, pairing of animals and confirmation of pregnancies is generally left to commercial suppliers, as in house breeding can be laborious and unpredictable. Here we describe a simple, reliable in-house breeding protocol for the generation of accurately-staged embryos as assessed by measurements of average crown to rump length (CRL).
  Cell Transplantation 05/2009;
• Article: Transplantation of allogeneic and xenogeneic placenta-derived cells reduces bleomycin-induced lung fibrosis.

  Anna Cargnoni, Lucia Gibelli, Alessandra Tosini, Patrizia Signoroni, Claudia Nassuato, Davide Arienti, Guerino Lombardi, Alberto Albertini, Georg Wengler, Ornella Parolini
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  ABSTRACT: Fetal membranes (amnion and chorion) have recently raised significant attention as potential sources of stem cells. We have recently demonstrated that cells derived from human term placenta show stem cell phenotype, high plasticity and display low immunogenicity both in vitro and in vivo. Moreover, placenta-derived cells, after xeno-transplantation, are able to engraft in solid organs including the lung. On these basis, we studied the effects of fetal membrane-derived cells on a mouse model of bleomycin-induced lung fibrosis. Fetal membrane-derived cells were infused 15 minutes after intra-tracheal bleomycin instillation. Different delivery routes were used: intra-peritoneal or intra-tracheal for both xenogenic and allogeneic cells, and intra-venous for allogeneic cells. The effects of the transplanted cells on bleomycin-induced inflammatory and fibrotic processes were then scored and compared between transplanted and control animals at different time points. By PCR and immunohistochemistry analysis, we demonstrated the presence of transplanted cells 3, 7, 9 and 14 days after transplantation. Concomitantly, we observed a clear decrease in neutrophil infiltration and a significant reduction in the severity of bleomycin-induced lung fibrosis in mice treated with placenta-derived cells, irrespective of the source (allogeneic or xenogeneic) or delivery route. Our findings constitute further evidence in support of the hypothesis that placenta-derived cells could be useful for clinical application, and warrant further studies toward the use of these cells for the repair of tissue damage associated with inflammatory and fibrotic degeneration.
  Cell Transplantation 05/2009;
• Article: A novel strategy incorporated the power of mesenchymal stem cells to allografts for segmental bone tissue engineering.

  Xiao Zou, Hong Cai, Zi Yin, Xiao Chen, Yang Jiang, Hu Hu, Hong Ouyang
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  ABSTRACT: Mesenchymal stem cells (MSCs) hold great promises for bone regeneration. However, the power of mesenchymal stem cells has not been incorporated to structural bone allografts in clinical practice. This study designed a new strategy to enhance the efficiency of allografts for segmental bone regeneration. Isolated MSCs were cultured to form a cell sheet. The MSCs sheet was then wrapped onto structural allografts. The assembled structures were cultured in vitro to evaluate the differentiation potential of MSCs sheet. Also the assembled structures were implanted subcutaneously into nude mice as well as into the segmental radius defect of rabbits to investigate the efficiency of MSC sheets to repopulate allografts for bone repair. MSCs sheets, upon assembling on bone grafts, showed similar differentiation properties to the in situ periosteum in vitro. After implantation the MSCs sheets accelerated the repopulation of bone grafts in nude mice. Moreover, MSCs sheets induced thicker cortical bone formation and more efficient graft-to-bone end fusion at the segmental bone defects in rabbits. This study thus presented a novel, more efficient and practical strategy for large weight-bearing bone reconstruction by using MSCs sheets to deliver large number of MSCs to repopulate the bone allografts.
  Cell Transplantation 05/2009;