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

Abstract

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

Keywords

• induced pluripotent stem cells
• kidney transplantation
• diabetes mellitus
• insulin secreting cells
• tacrolimus