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Implanted Cells (implanted + cell)
Selected AbstractsHuman islet-derived precursor cells can cycle between epithelial clusters and mesenchymal phenotypesJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009Behrous Davani Abstract We showed previously that undifferentiated, proliferating human islet-derived precursor cells (hIPCs) are a type of mesenchymal stem/stromal cell (MSC) that can be induced by serum deprivation to form clusters and ultimately differentiate in vitro to endocrine cells. We also demonstrated that partially differentiated hIPC clusters, when implanted under the kidney capsules of mice, continued to differentiate in vivo into hormone-producing cells. However, we noted that not all hIPC preparations yielded insulin-secreting cells in vivo and that in some animals no hormone-expressing cells were found. This suggested that the implanted cells were not always irreversibly committed to further differentiation and may even de-differentiate to a mesenchymal phenotype. In this study, we show that human cells with a mesenchymal phenotype are indeed found in the grafts of mice implanted with hIPCs in epithelial cell clusters (ECCs), which are obtained after 4-day in vitro culture of hIPCs in serum-free medium (SFM); mesenchymal cells were predominant in some grafts. We could mimic the transition of ECCs to de-differentiated mesenchymal cells in vitro by exposure to foetal bovine serum (FBS) or mouse serums, and to a significantly lesser extent to human serum. In a complementary series of experiments, we show that mouse serum and FBS are more effective stimulants of mesenchymal hIPC migration than is human serum. We found that proliferation was not needed for the transition from ECCs to de-differentiated cells because mitomycin-treated hIPCs that could not proliferate underwent a similar transition. Lastly, we show that cells exhibiting a mesenchymal phenotype can be found in grafts of adult human islets in mice. We conclude that epithelial-to-mesenchymal transition (EMT) of cells in hIPC ECCs can occur following implantation in mice. This potential for EMT of human islets or differentiated precursor cells must be considered in strategies for cell replacement therapy for diabetes. [source] Acceleration of cartilage repair by genetically modified chondrocytes over expressing bone morphogenetic protein-7JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2003Chisa Hidaka Background: Cartilage has a limited capacity to heal. Although chondrocyte transplantation is a useful therapeutic strategy, the repair process can be lengthy. Previously we have shown that over expression of bone morphogenetic protein-7 (BMP-7) in chondrocytes by adenovirus-mediated gene transfer leads to increased matrix synthesis and cartilage-like tissue formation in vitro. In this context we hypothesized that implantation of genetically modified chondrocytes expressing BMP-7 would accelerate the formation of hyaline-like repair tissue in an equine model of cartilage defect repair. Methods: Chondrocytes treated with adenovirus vector encoding BMP-7 (AdBMP-7) or as control, an adenovirus vector encoding an irrelevant gene (Escherichia coli cytosine deaminase, AdCD) were implanted into extensive (15 mm diameter) articular cartilage defects in the patellofemoral joints of 10 horses. Biopsies were performed to evaluate early healing at 4 weeks. At the terminal time point of 8 months, repairs were assessed for morphology, MRI appearance, compressive strength, biochemical composition and persistence of implanted cells. Results: Four weeks after surgery AdBMP-7-treated repairs showed an increased level of BMP-7 expression and accelerated healing, with markedly more hyaline-like morphology than control. Quantitative real-time polymerase chain reaction (PCR) analysis of the repair tissue 8 months after surgery showed that few implanted cells persisted. By this time, the controls had healed similarly to the AdBMP-7-treated defects, and no difference was detected in the morphologic, biochemical or biomechanical properties of the repair tissues from the two treatment groups. Conclusions: Implantation of genetically modified chondrocytes expressing BMP-7 accelerates the appearance of hyaline-like repair tissue in experimental cartilage defects. Clinical relevance: Rehabilitation after cell-based cartilage repair can be prolonged, leading to decreased patient productivity and quality of life. This study shows the feasibility of using genetically modified chondrocytes to accelerate cartilage healing. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Enhanced treatment of articular cartilage defect of the knee by intra-articular injection of Bcl-xL-engineered mesenchymal stem cells in rabbit modelJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 2 2010Bin Hu Abstract Direct intra-articular injection of mesenchymal stem cells (MSCs) has been proposed as a potential cell therapy for cartilage defects. This cell therapy relies on the survival of the implanted MSCs. However, the arduous local environment may limit cell viability after implantation, which would restrict the cells' regenerative capacity. Thus, it is necessary to reinforce the implanted cells against the unfavourable microenvironment in order to improve the efficacy of cell therapy. We examined whether the transduction of an anti-apoptotic protein, Bcl-xL, into MSCs could prevent cell death and improve the implantation efficiency of MSCs in a rabbit model. Our current findings demonstrate that the group treated with Bcl-xL-engineered MSCs could improve cartilage healing both morphologically and histologically when compared with the controls. These results suggest that intra-articular injection of Bcl-xL-engineered MSCs is a potential non-invasive therapeutic method for effectively treating cartilage defects of the knee. Copyright © 2009 John Wiley & Sons, Ltd. [source] Bone Marrow-Derived Cells Implanted into Freeze-Injured Urinary Bladders Reconstruct Functional Smooth Muscle LayersLUTS, Issue 1 2010Tetsuya IMAMURA Regenerative medicine offers great hope for lower urinary tract dysfunctions due to irreversibly damaged urinary bladders and urethras. Our aim is the utilization of bone marrow-derived cells to reconstruct smooth muscle layers for the treatments of irreversibly damaged lower urinary tracts. In our mouse model system for urinary bladder regeneration, the majority of smooth muscle layers in about one-third of the bladder are destroyed by brief freezing. Three days after wounding, we implant cultured cells derived from bone marrow. The implanted bone marrow-derived cells survive and differentiate into layered smooth muscle structures that remediate urinary dysfunction. However, bone marrow-derived cells implanted into the intact normal urinary bladders do not exhibit these behaviors. The presence of large pores in the walls of the freeze-injured urinary bladders is likely to be helpful for a high rate of survival of the implanted cells. The pores could also serve as scaffolding for the reconstruction of tissue structures. The surviving host cells upregulate several growth factor mRNAs that, if translated, can promote differentiation of smooth muscle and other cell types. We conclude that the multipotency of the bone marrow-derived cells and the provision of scaffolding and suitable growth factors by the microenvironment enable successful tissue engineering in our model system for urinary bladder regeneration. In this review, we suggest that the development of regenerative medicine needs not only a greater understanding of the requirements for undifferentiated cell proliferation and targeted differentiation, but also further knowledge of each unique microenvironment within recipient tissues. [source] Caspase inhibition increases survival of neural stem cells in the gastrointestinal tractNEUROGASTROENTEROLOGY & MOTILITY, Issue 4 2005M.-a . Micci Abstract, Neural stem cell (NSC) transplantation is a promising tool for the restoration of the enteric nervous system in a variety of motility disorders. Post-transplant survival represents a critical limiting factor for successful repopulation. The aim of this study was to determine the role of both immunological as well as non-immune-mediated mechanisms on post-transplant survival of NSC in the gut. Mouse CNS-derived NSC (CNS-NSC) were transplanted into the pylorus of recipient mice with and without the addition of a caspase-1 inhibitor (Ac-YVAD-cmk) in the injection media. In a separate experiment, CNS-NSC were transplanted in the pylorus of mice that were immunosuppressed by administration of cyclosporin A (CsA). Apoptosis and proliferation of the implanted cells was assessed 1 and 7 days post-transplantation. Survival was assessed 1 week post-transplantation. The degree of immunoresponse was also measured. The addition of a caspase-1 inhibitor significantly reduced apoptosis, increased proliferation and enhanced survival of CNS-NSC. CsA-treatment did not result in improved survival. Our results indicate that caspase-1 inhibition, but not immunosuppression, improves survival of CNS-NSC in the gut. Pre-treatment with a caspase-1 inhibitor may be a practical method to enhance the ability of transplanted CNS-NSC to survive in their new environment. [source] Age Dependence of the Human Skeletal Muscle Stem Cell in Forming Muscle TissueARTIFICIAL ORGANS, Issue 3 2006Ralf Schäfer Abstract:, Human skeletal muscle stem cells from healthy donors aged 2,82 years (n = 13) and from three children suffering from Duchenne Muscular Dystrophy (DMD) were implanted into soleus muscles of immunoincompetent mice and were also expanded in vitro until senescence. Growth of implanted cells was quantified by structural features and by the amount of human DNA present in a muscle. Proliferative capacity in vitro and in vivo was inversely related to age of the donor. In vitro, a decline of about two mean population doublings (MPDs) per 10 years of donor's age was observed. Muscle stem cells from DMD children were prematurely aged. In general, cell preparations with low or decreasing content in desmin-positive cells produced more MPDs than age-matched high-desmin preparations and upon implantation more human DNA and more nonmyogenic than myogenic tissue. Thus, a "Desmin Factor" was derived which predicts "quality" of the human muscle tissue growing in vivo. This factor may serve as a prognostic tool. [source] | ||||||||||