Potential Role Of Bone Marrow Mesenchymal Stem Cells On Islet Transplantation

Objective: To investigate potential effect of bone marrow mesenchymal stem cells (MSCs) on islet transplantation.Methods: (1) Murine bone marrow mesenchymal stem cells were isolated, cultured, expanded and identified. An economic, efficient, stable islet isolation method and a stable islet transplantation model were established. (2) Mesenchymal stem cells were isolated from murine bone marrow and expanded ex vivo. Marginal quantity of murine islets were syngeneically transplanted beneath the kidney capsule of STZ-induced diabetic mice with or without MSCs. Glucose and body weight were routinely monitored after transplantation. Intraperitoneal glucose tolerance test (IPGTT) was performed one month later and subsequently kidneys bearing the graft were retrieved for immunohistochemistry study. (3)Bone marrow mesenchymal stem cells were isolated and expanded from both BALB/c and ICR mice. Sufficient amount of ICR islets were transplanted together with either BALB/c-derived or ICR-derived bone marrow MSCs. Blood glucose and body weight were routinely monitored. Kidneys bearing islets were retreived for ilnmunohistochemistry study after rejection. Results: (1) MSCs could differentiate into osteocytes and adipocytes after induction. The expression of CD29, CD34, CD45 and CD90 were (93.86±1.12)%, (0.48±0.38) %, (1.89±1.49) %, (94.11±3.32) %, respectively. Ficoll and Histopaque were similar in islet purification, both yielding stable amount of islets with good viability, transplantation of which resulted in sustained norrnglycemia in STZ-induced diabetic mice. (2) Islet transplantantion together with MSCs resulted in a significantly higher percentage of mice cured from diabetes(71.4% vs 42.9%, P＜0.05) and better glucose tolerance. Blood glucose went up again after removal of the kidney bearing islets. The graft was stained strongly positive for insulin. But no endothelial markers were found. No transdifferentiation of MSCs was observed. (3) Cotransplantation with donor or recipient-derived bone marrow MSCs failed to prolong the normglycemic period after allogeneic transplantaion(P＞0.05). Widespread lymphocytic infiltration beneath the kidney capsule was observed and insulin staining was quite weak, despite relatively long term survival of MSCs.Conclusion: Mesenchymal stem cells could exert a protective effect on syngeneic islet transplantation and reduce the amount of islets required for single successful islet transplantation. However, No significant immunomodulatory effect of MSCs in allogeneic islet transplantation was observed in our experiment.