Congenic mesenchymal stem cell therapy reverses hyperglycemia in experimental type 1 diabetes
Objective: A number of clinical trials are underway to test whether mesenchymal stem cells (MSC) are effective in treating various diseases, including type 1 diabetes (T1D). Although this cell therapy holds great promise, the optimal source of MSC has yet to be determined with respect to MHC matching. Here, we examine this question by testing the ability of congenic MSC, obtained from the NOR mouse strain, to reverse recent-onset T1D in NOD mice, as well as determine the immunomodulatory effects of NOR MSC in vivo.
Research Design and Methods: NOR MSC were evaluated with regard to their in vitro immunomodulatory function in the context of autoreactive T cell proliferation and dendritic cell (DC) generation. The in vivo effect of NOR MSC therapy on reversal of recent-onset hyperglycemia and on immunogenic cell subsets in NOD mice was also examined.
Results: NOR MSC were shown to suppress diabetogenic T cell proliferation via PD-L1 and to suppress generation of myeloid/inflammatory DC predominantly through an IL-6-dependent mechanism. NOR MSC treatment of experimental T1D resulted in long-term reversal of hyperglycemia, and therapy was shown to alter diabetogenic cytokine profile, to diminish T cell effector frequency in the pancreatic lymph nodes, to alter antigen-presenting cell frequencies, and to augment the frequency of the plasmacytoid subset of DC.
Conclusions: These studies demonstrate the inimitable benefit of congenic MSC therapy in reversing experimental T1D. These data should benefit future clinical trials using MSC as treatment for T1D.
- Received April 16, 2010.
- Accepted September 1, 2010.
- Copyright © American Diabetes Association