Ayman F. Refaie, Mahmoud M. Gabr, Mahmoud M. Zakaria, Sherry M. Khater, Sylvia A. Ashamallah, Amani M. Ismail, and Mohamed A. Ghoneim.Urology and Nephrology Center, Mansoura, Egypt
Harvesting, expansion, and directed differentiation of human bone marrow-derived mesenchymal stem cells (BM-MSCs) could provide an autologous source of surrogate β-cells that would alleviate the limitations of availability and/or allogenic rejection following pancreatic or islet transplantation. Herein, the evolution and achievements of stem cell research for treatment of diabetes mellitus at Mansoura Urology & Nephrology Center, Egypt will be presented.
First, we were able to generate insulin-producing cells (IPCs) from adult human BM-MSCs. These cells were capable of correcting hyperglycemia in diabetic nude mice.
Second, we compared the relative efficacy of three differentiation protocols: conophylline-based (one-step protocol), trichostatin-A-based (two-step protocol), and β-mercaptoethanol-based (three-step protocol). The yield of functional IPCs following directed differentiation of HBM-MSCs was comparable among the three tested protocols. However, trichostatin-A-based protocol is preferred in view of its simplicity and the short duration needed for differentiation.
Third, we provided evidences of further in vivo maturation/differentiation of BM-MSCs. Four weeks after transplantation, the proportion of IPCs increased by 10-fold. All relevant pancreatic endocrine genes were expressed, and their expression levels were significantly increased in vivo.
Conclusion: in spite of these achievements, several questions remain: how long will these cells retain their function? What is the optimal site for their transplantation? What are the risks of teratogenicity? Once these questions are adequately addressed, meaningful clinical applications can be developed.