scholarly journals Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells into Insulin-Producing Cells: Evidence for Further Maturation In Vivo

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Mahmoud M. Gabr ◽  
Mahmoud M. Zakaria ◽  
Ayman F. Refaie ◽  
Sherry M. Khater ◽  
Sylvia A. Ashamallah ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Trichostatin A ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Insulin Producing Cells ◽  
Parallel Increase

The aim of this study was to provide evidence for further in vivo maturation of insulin-producing cells (IPCs) derived from human bone marrow-derived mesenchymal stem cells (HBM-MSCs). HBM-MSCs were obtained from three insulin-dependent type 2 diabetic volunteers. Following expansion, cells were differentiated according to a trichostatin-A/GLP protocol. One million cells were transplanted under the renal capsule of 29 diabetic nude mice. Blood glucose, serum human insulin and c-peptide levels, and glucose tolerance curves were determined. Mice were euthanized 1, 2, 4, or 12 weeks after transplantation. IPC-bearing kidneys were immunolabeled, number of IPCs was counted, and expression of relevant genes was determined. At the end of in vitro differentiation, all pancreatic endocrine genes were expressed, albeit at very low values. The percentage of IPCs among transplanted cells was small (≤3%). Diabetic animals became euglycemic8±3days after transplantation. Thereafter, the percentage of IPCs reached a mean of ~18% at 4 weeks. Relative gene expression of insulin, glucagon, and somatostatin showed a parallel increase. The ability of the transplanted cells to induce euglycemia was due to their further maturation in the favorable in vivo microenvironment. Elucidation of the exact mechanism(s) involved requires further investigation.

Generation of insulin producing cells from human bone marrow-derived mesenchymal stem cells: further in vivo maturartion.

Cytotherapy ◽  
2014 ◽  
Vol 16 (4) ◽  
pp. S81
Author(s):  
A.F. Refaie ◽  
M.M. Gabr ◽  
M.M. Zakaria ◽  
S. m. Khater ◽  
S.A. Ashamallah ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Insulin Producing Cells

Purified Human Bone Marrow Multipotent Mesenchymal Stem Cells Regenerate Infarcted Myocardium in Experimental Rats

2005 ◽  
Vol 14 (10) ◽  
pp. 787-798 ◽  
Author(s):  
Shaoheng Zhang ◽  
Zhuqing Jia ◽  
Junbo Ge ◽  
Lizhong Gong ◽  
Yanling Ma ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Left Ventricular ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Vegf Expression ◽  
Confocal Immunofluorescence Microscopy

Recent findings suggest the feasibility of cardiac repair by transplantation of bone marrow mesenchymal stem cell (MSCs). However, it remains controversial regarding which cell type is the best source for transplanting into the ischemic heart because of lack of well-defined cell markers. In this study, we investigated the in vitro and in vivo effects of the novel multipotent marrow mesenchymal stem cells (MMSCs) from human bone marrow. Pluripotent markers (Oct4, Bmi1, and Abcg2) and vascular endothelial growth factor (VEGF) were detected by RT-PCR and immunofluorescence in MMSCs. Myocardial differentiation was induced in the expanded MMSC cultures by treatment with 5-azacyline. Expressions of VEGF in the animals transplanted with MMSCs were markedly increased in comparison with the animals injected with fibroblasts or saline at both mRNA and protein levels. VEGF expression was observed in both transplanted MMSCs and recipient cardiomyocytes by immunofluorescence. Confocal immunofluorescence microscopy revealed the specific markers for cardiomyocytes and endothelial cells in transplanted MMSCs 14 days after transplantation. Vessel count was increased and left ventricular function improved post-MMSC transplantation. These results indicate that transplantation of purified MMSCs from human bone marrow upregulated VEGF expression, enhanced angiogenesis, and improved the functional recovery following myocardial infarction in rats.

scholarly journals Engineering adipose-like tissue in vitro and in vivo utilizing human bone marrow and adipose-derived mesenchymal stem cells with silk fibroin 3D scaffolds

Biomaterials ◽  
2007 ◽  
Vol 28 (35) ◽  
pp. 5280-5290 ◽  
Author(s):  
Joshua R. Mauney ◽  
Trang Nguyen ◽  
Kelly Gillen ◽  
Carl Kirker-Head ◽  
Jeffrey M. Gimble ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Silk Fibroin ◽  
Human Bone ◽  
Human Bone Marrow ◽  
3D Scaffolds

scholarly journals Generation of Insulin-Producing Cells from Human Bone Marrow-Derived Mesenchymal Stem Cells: Comparison of Three Differentiation Protocols

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Mahmoud M. Gabr ◽  
Mahmoud M. Zakaria ◽  
Ayman F. Refaie ◽  
Sherry M. Khater ◽  
Sylvia A. Ashamallah ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Trichostatin A ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Diabetic Patients ◽  
Directed Differentiation ◽  
C Peptide ◽  
Insulin Producing Cells

Introduction. Many protocols were utilized for directed differentiation of mesenchymal stem cells (MSCs) to form insulin-producing cells (IPCs). We compared the relative efficiency of three differentiation protocols.Methods. Human bone marrow-derived MSCs (HBM-MSCs) were obtained from three insulin-dependent type 2 diabetic patients. Differentiation into IPCs was carried out by three protocols: conophylline-based (one-step protocol), trichostatin-A-based (two-step protocol), andβ-mercaptoethanol-based (three-step protocol). At the end of differentiation, cells were evaluated by immunolabeling for insulin production, expression of pancreatic endocrine genes, and release of insulin and c-peptide in response to increasing glucose concentrations.Results. By immunolabeling, the proportion of generated IPCs was modest (≃3%) in all the three protocols. All relevant pancreatic endocrine genes, insulin, glucagon, and somatostatin, were expressed. There was a stepwise increase in insulin and c-peptide release in response to glucose challenge, but the released amounts were low when compared with those of pancreatic islets.Conclusion. The yield of functional IPCs following directed differentiation of HBM-MSCs was modest and was comparable among the three tested protocols. Protocols for directed differentiation of MSCs need further optimization in order to be clinically meaningful. To this end, addition of an extracellular matrix and/or a suitable template should be attempted.

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