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KMID : 1102220240430020236
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Kidney Research and Clinical Practice
2024 Volume.43 No. 2 p.236 ~ p.249
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Prediction of diabetes mellitus after kidney transplantation using patient-specific induced pluripotent stem cells
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Lim Sun-Woo
Shin Yoo-Jin
Sheng Cui
Ko Eun-Jeong
Chung Byung-Ha
Yang Chul-Woo
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Abstract
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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.
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KEYWORD
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Induced pluripotent stem cells, Kidney transplantation, Diabetes mellitus, Insulin secreting cells, Tacrolimus
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