Prediction of diabetes mellitus development after kidney transplantation using patient-specific induced pluripotent stem cells

Abstract

Abstract Background: Multiple risk factors are involved in new-onset diabetes mellitus after transplantation; however, their prediction of clinical prognosis remains unclear. Therefore, we investigated whether patient-specific induced pluripotent stem cells (iPSCs) could help predict diabetes mellitus (DM) development before performing kidney transplantation (KT). Methods: We first examined whole transcriptome and functional enrichment analyses of KT patient-derived iPSCs and revealed that insulin resistance, type 2 DM, and transforming growth factor-beta signaling pathways are associated between the group of DM and non-DM. We next determined whether the different genetic background was associated with development from iPSC into pancreatic progenitor (PP) cells. Results: We found that the level of differentiation-related key markers of PP cells was significantly lower in the DM group than in the non-DM group. Moreover, the results of tacrolimus toxicity screening showed significant decrease in the number of PP cells of DM group compared with the non-DM group, suggesting that these cells are more susceptible to tacrolimus toxicity. Conclusions: Taken together, the PP cells of the DM group showed low developmental potency, which was accompanied by a significantly different genetic background compared with the non-DM group. Thus, genetic analysis can be used to predict the risk of developing DM before performing KT.