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使用患者特异性诱导多能干细胞预测肾移植后糖尿病

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

作者信息

Lim Sun Woo, Shin Yoo Jin, Cui Sheng, Ko Eun Jeong, Chung Byung Ha, Yang Chul Woo

机构信息

Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Transplant Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

出版信息

Kidney Res Clin Pract. 2024 Mar;43(2):236-249. doi: 10.23876/j.krcp.22.251. Epub 2023 Jun 15.

DOI:10.23876/j.krcp.22.251
PMID:37448282
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11016675/
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.

摘要

背景

器官移植后新发糖尿病（DM）涉及多种危险因素；然而，它们预测临床预后的能力仍不明确。因此，我们研究了患者特异性诱导多能干细胞（iPSC）是否有助于在进行肾移植（KT）前预测DM的发生。

方法

我们首先对KT患者来源的iPSC进行了全转录组和功能富集分析。我们的结果显示，胰岛素抵抗、2型DM和转化生长因子β信号通路在DM组和非DM组之间存在关联。接下来，我们确定遗传背景是否与iPSC向胰腺祖细胞（PP）的分化有关。

结果

DM组中PP细胞分化相关关键标志物的水平显著低于非DM组。此外，他克莫司毒性筛选结果显示，与非DM组相比，DM组PP细胞数量显著减少，表明这些细胞对他克莫司毒性更敏感。

结论

综上所述,这些结果表明，与非DM组相比，DM组的PP细胞发育潜能较低，且伴有显著不同的遗传背景。因此，基因分析可用于预测KT前DM的风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/398f/11016675/b9c93bb8fec3/j-krcp-22-251f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/398f/11016675/cb7cad534712/j-krcp-22-251f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/398f/11016675/15cba95b4211/j-krcp-22-251f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/398f/11016675/a439d480b314/j-krcp-22-251f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/398f/11016675/53501fe99f95/j-krcp-22-251f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/398f/11016675/af646e5b10c6/j-krcp-22-251f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/398f/11016675/37cefd91d711/j-krcp-22-251f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/398f/11016675/37c17bb4fbf2/j-krcp-22-251f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/398f/11016675/4f705af04c02/j-krcp-22-251f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/398f/11016675/b9c93bb8fec3/j-krcp-22-251f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/398f/11016675/cb7cad534712/j-krcp-22-251f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/398f/11016675/15cba95b4211/j-krcp-22-251f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/398f/11016675/a439d480b314/j-krcp-22-251f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/398f/11016675/53501fe99f95/j-krcp-22-251f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/398f/11016675/af646e5b10c6/j-krcp-22-251f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/398f/11016675/37cefd91d711/j-krcp-22-251f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/398f/11016675/37c17bb4fbf2/j-krcp-22-251f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/398f/11016675/4f705af04c02/j-krcp-22-251f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/398f/11016675/b9c93bb8fec3/j-krcp-22-251f9.jpg

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