Adipose-derived MSCs Treatment of Diabetes and Diabetic Bladder Dysfunction
The overall goals of this application are to examine the time-dependence and potential mechanisms of action of adipose-derived mesenchymal stem cells (aMSCs) in the treatment of diabetes mellitus and diabetic bladder dysfunction (DBD). Novel treatments are required for DBD, one of the most common, costly, and yet understudied complications of diabetes. Based on published research and our preliminary data, we hypothesize that administration of aMSCs can reverse the hyperglycemia in streptozotocin-induced type 1 diabetes in a time-dependent manner, having an effect when sufficient insulin-producing cells still remain, but not after long-term, sustained damage. Moreover, we hypothesize that aMSCs can improve DBD to some extent even when the hyperglycemia is not reversed. We further hypothesize that therapeutic effects of aMSCs can be exerted via a paracrine-mediated mechanism, and that administration of conditioned mediumfrom aMSCs can reverse or improve hyperglycemia and DBD. Finally, we hypothesize that culturing aMSCs with serum from diabetic rats will enhance the therapeutic benefit of the CM compared with culturing aMSCswith regular serum, due to the presence of “tissue damage-related” factors in diabetic rat serum that will stimulate aMSCs to secrete specific “tissue repair” factors. Through the Diabetic Complications ConsortiumPilot & Feasibility funding mechanism we propose to test those hypotheses by conducting the following Specific Aims: 1) To examine the effects of aMSCs on hyperglycemia reversal and DBD at different diabetesstages in STZ-induced diabetic rats. 2) To compare the effects of administration of aMSCs vs. conditioned medium from aMSCs cultured with standard fetal bovine serum, normal rat serum, or diabetic rat serum, onhyperglycemia and DBD in STZ-induced diabetic rats. The results of this study will provide important insights into a potential new therapy for patients with DBD. RELEVANCE

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