Mesenchymal Stem Cells Promoted Long-Term Graft Survival of Xenogenic Mouse Islet Cells in Recipient Mice.

INTRODUCTION: In clinical islet transplantation, immunologic rejection is a major factor contributing to the poor engraftment of the islets. More recently, experimental evidence and preliminary clinical studies have demonstrated that mesenchymal stem cells (MSCs) have an important immune modulatory function. Here we described that co-transplantation of islet cells and donor MSCs from Balb/c mice promoted long-term graft survival of transplanted islet cells in recipient mice with diabetes.

METHODS: Bone marrow MSCs of adult Balb/c mice were cultured, and characterized by surface molecules, the typical spindle-shaped morphology, and the ability of differentiation, and islet cells were isolated by the collagenase digestion method. After MSCs (10 ⁵ ) were transplanted via the tail vein into C57BL/6 recipient mice with diabetes induced by streptozotocin, mixed MSCs and islet cells (1000:500) were injected under the kidney capsules. To assess whether MSCs downregulated T- cell responses in vivo, the histological examination by light microscape was performed, and status of blood T-lymphocytes by flow cytometry and immunofluorescence. Before and after transplantation, blood insulin and glucose levels were monitored.

RESULTS: 7 days after transplantation, blood insulin and glucose levels in recipient mice injected with both islet cells and donor MSCs were (30.6±5.1)U/L and (6.9±0.4)mmol/L, respectively, whereas those in mice injected with islet cells alone were (19.8±4.9)U/L and (9.9±0.6)mmol/L, respectively. Moreover, Flow cytometry showed that expression of the activation markers CD25, CD69, and IFN-γ on CD4 or CD8 T cells increased significantly in latter. 6 wk after transplantation, blood insulin and glucose levels in the former still were normal, but not in latter. The histological examination showed that there was inflammation in latter, but not any morphological destructed evidence in former. The hormone release from islet cells-MSCs mixed grafts was a complete functional recovery.

CONCLUSION: Our results indicated that MSCs suppressed allogeneic T- cell responses in vivo, and MSCs promoted long-term graft survival of transplanted islet cells in recipient mice with diabetes.