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

Author:

Gabr Mahmoud M.1,Zakaria Mahmoud M.1,Refaie Ayman F.2,Khater Sherry M.3,Ashamallah Sylvia A.3,Ismail Amani M.4,El-Halawani Sawsan M.1,Ghoneim Mohamed A.5

Affiliation:

1. Department of Biotechnology, Urology and Nephrology Center, Mansoura 35516, Egypt

2. Department of Nephrology, Urology and Nephrology Center, Mansoura 35516, Egypt

3. Department of Pathology, Urology and Nephrology Center, Mansoura 35516, Egypt

4. Department of Immunology, Urology and Nephrology Center, Mansoura 35516, Egypt

5. Department of Urology, Urology and Nephrology Center, Mansoura 35516, Egypt

Abstract

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.

Funder

Misr El-Kheir Foundation

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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