In cases of patients with rapidly progressive diabetes mellitus (DM), autologous stem cell transplantation is considered as one of the regenerative treatments. However, whether the effects of autonomous stem cell transplantation on DM patients are equivalent to transplantation of stem cells derived from healthy persons is unclear. This study revealed that adipose-derived mesenchymal stem cells (ADSC) derived from type II DM patients had lower transplantation efficiency, proliferation potency, and stemness than those derived from healthy persons, leading to a tendency to induce apoptotic cell death. To address this issue, we conducted a cyclopedic mRNA analysis using a next-generation sequencer and identified G6PC3 and IGF1, genes related to the FoxO signaling pathway, as the genes responsible for lower performance. Moreover, it was demonstrated that the lower transplantation efficiency of ADSCs derived from type II DM patients might be improved by knocking down both G6PC3 and IGF1 genes. This study clarified the difference in transplantation efficiency between ADSCs derived from type II DM patients and those derived from healthy persons and the genes responsible for the lower performance of the former. These results can provide a new strategy for stabilizing the quality of stem cells and improving the therapeutic effects of regenerative treatments on autonomous stem cell transplantation in patients with DM.

Type 1 diabetes mellitus is characterized by the destruction of pancreatic β-cells and requires the regeneration of these destroyed pancreatic β-cells for radical treatment. The degeneration of organelles in stem cells compromises stem cell quality; however, organelles in the mesenchymal stem cells of patients with type 1 diabetes mellitus have not been characterized previously. In this study, we use transmission electron microscopy to evaluate the degeneration of organelles in adipose-derived stem cells of patients with type 1 diabetes mellitus (T1DM ADSCs). Compared to adipose-derived stem cells from healthy humans, T1DM ADSCs degenerate differently, characterized by prominent enlarged spherical vesicles. The exosomes of T1DM ADSCs are found to be enlarged, reduced in number, and increased in the percentage of those positive for tetraspanin CD9. The findings of this study provide insight into the characteristics of stem cells in patients with type 1 diabetes mellitus.

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