Insulin Producing Cells from Adipose Mesenchymal Stromal Origin as Implant Strategy in Diabetic Rats

Abstract

Type 1 diabetes mellitus (DM1) is an autoimmune disease characterized by the destruction of insulin-producing pancreatic β cells. Among the current experimental therapies, we highlight the use of transdifferentiated mesenchymal stromal cells (MSCs) into insulin-producing cells (IPCs). Here, we studied the strategy of implanting IPCs differentiated from adipose tissue MSCs in the subcutaneous region (SC) of rats to investigate their protection against hyperglycemia induced by streptozotocin. The first phase of this study (in vitro) was to characterize adipose-derived stromal cells (ADSCs) and to evaluate the protocol for their differentiation in IPCs. The second phase was to assess the functionality of IPCs in vivo three and eight weeks after implant. The cells were then implanted in SC after one-week DM1 model induction (Process: 30626). The implant improved hyperglycemia and reduced the serum content of advanced glycation end products (AGEs) in diabetic rats at three weeks, but this effect was not observed after the longer period of eight weeks, showing a transient effect. Serum C-peptide was not detected in the SC group, neither after three nor eight weeks of DM1 model. Regarding animal body weight, both diabetic and implanted rats maintained their weight over time, while the Sham group presented the natural increase related to the normal growth of the animal. Together, these data are promising but also need improvement in the effectiveness of the therapy, with future studies attempting implantation of a larger number of cells or multiple implants, since the subcutaneous access is not very invasive and easy to perform.