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血液透析患者诱导多能干细胞在肾脏再生中的再生潜能。

Regenerative potential of induced pluripotent stem cells derived from patients undergoing haemodialysis in kidney regeneration.

机构信息

Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.

Division of Regenerative Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.

出版信息

Sci Rep. 2018 Oct 8;8(1):14919. doi: 10.1038/s41598-018-33256-7.

DOI:10.1038/s41598-018-33256-7
PMID:30297790
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6175865/
Abstract

Kidney regeneration from pluripotent stem cells is receiving a lot of attention because limited treatments are currently available for chronic kidney disease (CKD). It has been shown that uremic state in CKD is toxic to somatic stem/progenitor cells, such as endothelial progenitor and mesenchymal stem cells, affecting their differentiation and angiogenic potential. Recent studies reported that specific abnormalities caused by the non-inherited disease are often retained in induced pluripotent stem cell (iPSC)-derived products obtained from patients. Thus, it is indispensable to first assess whether iPSCs derived from patients with CKD due to non-inherited disease (CKD-iPSCs) have the ability to generate kidneys. In this study, we generated iPSCs from patients undergoing haemodialysis due to diabetes nephropathy and glomerulonephritis (HD-iPSCs) as representatives of CKD-iPSCs or from healthy controls (HC-iPSCs). HD-iPSCs differentiated into nephron progenitor cells (NPCs) with similar efficiency to HC-iPSCs. Additionally, HD-iPSC-derived NPCs expressed comparable levels of NPC markers and differentiated into vascularised glomeruli upon transplantation into mice, as HC-iPSC-derived NPCs. Our results indicate the potential of HD-iPSCs as a feasible cell source for kidney regeneration. This is the first study paving the way for CKD patient-stem cell-derived kidney regeneration, emphasising the potential of CKD-iPSCs.

摘要

多能干细胞的肾脏再生受到广泛关注，因为目前慢性肾脏病 (CKD) 的治疗方法有限。已有研究表明，CKD 中的尿毒症状态对体干细胞/祖细胞（如内皮祖细胞和间充质干细胞）具有毒性，影响其分化和血管生成潜能。最近的研究报告称，由非遗传性疾病引起的特定异常通常会保留在患者来源的诱导多能干细胞 (iPSC) 衍生产品中。因此，首先评估是否可以获得由非遗传性疾病引起的 CKD 患者的 iPSC（CKD-iPSC）来生成肾脏是必不可少的。在这项研究中，我们以接受血液透析的糖尿病肾病和肾小球肾炎患者（HD-iPSC）为代表的 CKD-iPSC 或健康对照者（HC-iPSC）中生成了 iPSC。HD-iPSC 分化为肾祖细胞 (NPC) 的效率与 HC-iPSC 相似。此外，HD-iPSC 衍生的 NPC 在移植到小鼠中后表达类似水平的 NPC 标志物，并分化为血管化的肾小球，与 HC-iPSC 衍生的 NPC 一样。我们的研究结果表明 HD-iPSC 作为肾脏再生的可行细胞来源具有潜力。这是首例为 CKD 患者干细胞衍生肾脏再生铺平道路的研究，强调了 CKD-iPSC 的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd22/6175865/1e72345ef186/41598_2018_33256_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd22/6175865/30b8157ca492/41598_2018_33256_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd22/6175865/cfae5cb884dd/41598_2018_33256_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd22/6175865/64e9094ffcab/41598_2018_33256_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd22/6175865/03deb9b55d99/41598_2018_33256_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd22/6175865/1e72345ef186/41598_2018_33256_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd22/6175865/30b8157ca492/41598_2018_33256_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd22/6175865/cfae5cb884dd/41598_2018_33256_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd22/6175865/64e9094ffcab/41598_2018_33256_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd22/6175865/03deb9b55d99/41598_2018_33256_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd22/6175865/1e72345ef186/41598_2018_33256_Fig5_HTML.jpg

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