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利用诱导多能干细胞进行糖尿病疾病建模与药物发现的最新进展

Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells.

作者信息

Kawser Hossain Mohammed, Abdal Dayem Ahmed, Han Jihae, Kumar Saha Subbroto, Yang Gwang-Mo, Choi Hye Yeon, Cho Ssang-Goo

机构信息

Department of Animal Biotechnology, Animal Resources Research Center, and Incurable Disease Animal Model and Stem Cell Institute (IDASI), Konkuk University, Gwangjin-gu, Seoul 05029, Korea.

出版信息

Int J Mol Sci. 2016 Feb 19;17(2):256. doi: 10.3390/ijms17020256.

DOI:10.3390/ijms17020256
PMID:26907255
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4783985/
Abstract

Diabetes mellitus (DM) is a widespread metabolic disease with a progressive incidence of morbidity and mortality worldwide. Despite extensive research, treatment options for diabetic patients remains limited. Although significant challenges remain, induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any cell type, including insulin-secreting pancreatic β cells, highlighting its potential as a treatment option for DM. Several iPSC lines have recently been derived from both diabetic and healthy donors. Using different reprogramming techniques, iPSCs were differentiated into insulin-secreting pancreatic βcells. Furthermore, diabetes patient-derived iPSCs (DiPSCs) are increasingly being used as a platform to perform cell-based drug screening in order to develop DiPSC-based cell therapies against DM. Toxicity and teratogenicity assays based on iPSC-derived cells can also provide additional information on safety before advancing drugs to clinical trials. In this review, we summarize recent advances in the development of techniques for differentiation of iPSCs or DiPSCs into insulin-secreting pancreatic β cells, their applications in drug screening, and their role in complementing and replacing animal testing in clinical use. Advances in iPSC technologies will provide new knowledge needed to develop patient-specific iPSC-based diabetic therapies.

摘要

糖尿病(DM)是一种广泛存在的代谢性疾病,在全球范围内其发病率和死亡率呈上升趋势。尽管进行了广泛研究,但糖尿病患者的治疗选择仍然有限。尽管仍存在重大挑战,但诱导多能干细胞(iPSC)有能力分化为任何细胞类型,包括分泌胰岛素的胰腺β细胞,这凸显了其作为糖尿病治疗选择的潜力。最近已从糖尿病和健康供体中获得了多个iPSC系。利用不同的重编程技术,iPSC被分化为分泌胰岛素的胰腺β细胞。此外,源自糖尿病患者的iPSC(DiPSC)越来越多地被用作进行基于细胞的药物筛选的平台,以开发针对糖尿病的基于DiPSC的细胞疗法。基于iPSC衍生细胞的毒性和致畸性测定还可以在将药物推进到临床试验之前提供有关安全性方面的更多信息。在本综述中,我们总结了将iPSC或DiPSC分化为分泌胰岛素的胰腺β细胞的技术开发的最新进展、它们在药物筛选中的应用以及它们在临床应用中补充和替代动物试验方面的作用。iPSC技术的进步将为开发基于患者特异性iPSC的糖尿病疗法提供所需的新知识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/538a/4783985/634e520568d1/ijms-17-00256-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/538a/4783985/58e94bd94361/ijms-17-00256-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/538a/4783985/634e520568d1/ijms-17-00256-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/538a/4783985/58e94bd94361/ijms-17-00256-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/538a/4783985/634e520568d1/ijms-17-00256-g002.jpg

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