Mesenchymal stem cells (MSCs) not only serve as a cell reservoir, replacing damaged cells, but also as a “drug store”, providing trophic factors that exert multiple potent cellular effects, such as anti-apoptotic, anti-fibrotic, anti-inflammatory, and immunomodulatory. There is increasing evidence that MSC trophic factors are able to improve the ability of β-cells to secrete insulin in vitro and promote islet graft survival in vivo. Here, we report that co-transplantation of freshly isolated islets with adipose-derived mesenchymal stem cells (Ad-MSCs) results in a rapid, significant reduction in hyperglycemia in streptozotocin (STZ)-induced diabetic rats. Lewis rats (n=30) were injected intraperitoneally with STZ (80 mg/kg); by day 3 post-injection, 24 animals (∼80%) achieved elevated blood glucose levels that stabilized at ∼300 mg/dL. On day 14, STZ-treated rats received the following transplants via hepatic portal vein infusion: PBS (negative controls), Lewis (isografts) or Fischer (allografts) islets alone or combined with Lewis rat Ad-MSCs. Initially, co-transplantation of islets (isografts or allografts) with Ad-MSCs dramatically reduced blood glucose levels compared to transplantation of islets alone (∼60% vs. ∼30%). However, only isografts combined with Ad-MSCs promoted the retention of transplanted islet function, resulting in the maintenance of blood glucose levels at ∼47% of the pre-transplantation level (=100%) through 70 days post-transplantation. Morphologically, these co-transplants in liver were larger in size, had more capillaries, and produced more insulin than islets alone. Although islets (iso- or allo-grafts) co-transplanted with Ad-MSCs appeared to provide an accelerated normalization of blood glucose levels, no evidence was found that allograft rejection was reduced. We conclude that co-transplantation improved islet viability more, with a prolonged anti-hyperglycemic effect, than islets alone.

Disclosure

X. Chen: None. S. Li: None. H. Wang: None.

Funding

San Antonio Medical Foundation

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