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再生医学中治疗糖尿病的当前方法:引入CRISPR/CAS9技术及非胚胎干细胞疗法的实例

Current approaches in regenerative medicine for the treatment of diabetes: introducing CRISPR/CAS9 technology and the case for non-embryonic stem cell therapy.

作者信息

Coombe Lauren, Kadri Aamir, Martinez Jessica Ferrer, Tatachar Vivas, Gallicano Gary Ian

机构信息

Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center 3900 Reservoir Road NW, Washington DC 20007, USA.

出版信息

Am J Stem Cells. 2018 Dec 1;7(5):104-113. eCollection 2018.

PMID:30697454
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6334205/
Abstract

Type 1 diabetes mellitus (T1DM) is an autoimmune disorder in which the body destroys its pancreatic β cells. Since these cells are responsible for insulin production, dysfunction or destruction of these cells necessitates blood glucose control through exogenous insulin shots. Curative treatment involves pancreas transplantation, but due to the incidence of transplant rejection and complications associated with immunosuppression, alternatives are being explored. Despite facing clinical challenges and issues with public perception, the field of regenerative stem cell therapy shows great promise for the treatment of diabetes. The idea of harnessing pluripotency to derive cells and tissues with characteristics of choice is astounding but feasible, and this review seeks to determine which method of stem cell derivation is preferable for diabetes treatment. In this report, we outline the methods for deriving human embryonic stem cells (hESCs), induced pluripotent stem cells (iPSCs), and adult stem cells or progenitor cells to generate functional islet cells and related tissues. We discuss the specific uses and advantages of each method, and we comment on the ethics and public perceptions surrounding these methods and how they may affect the future of stem cell research. For the reasons outlined in this paper, we believe that non-embryonic stem cell lines, including iPSCs, somatic cell nuclear transfer lines, and adult tissue derived stem cells, offer the highest therapeutic potential for treating diabetes.

摘要

1型糖尿病(T1DM)是一种自身免疫性疾病,机体破坏自身胰腺β细胞。由于这些细胞负责胰岛素的产生,这些细胞的功能障碍或破坏需要通过注射外源性胰岛素来控制血糖。根治性治疗包括胰腺移植,但由于移植排斥反应的发生率以及与免疫抑制相关的并发症,人们正在探索替代方法。尽管面临临床挑战和公众认知方面的问题,但再生干细胞治疗领域在糖尿病治疗方面显示出巨大的潜力。利用多能性来获得具有所需特性的细胞和组织的想法令人震惊但切实可行,本综述旨在确定哪种干细胞衍生方法更适合糖尿病治疗。在本报告中,我们概述了获得人类胚胎干细胞(hESC)、诱导多能干细胞(iPSC)以及成体干细胞或祖细胞以生成功能性胰岛细胞和相关组织的方法。我们讨论了每种方法的具体用途和优势,并对围绕这些方法的伦理和公众认知以及它们可能如何影响干细胞研究的未来发表评论。基于本文所述的原因,我们认为非胚胎干细胞系,包括iPSC、体细胞核移植系和成体组织来源的干细胞,在治疗糖尿病方面具有最高的治疗潜力。

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Current approaches in regenerative medicine for the treatment of diabetes: introducing CRISPR/CAS9 technology and the case for non-embryonic stem cell therapy.再生医学中治疗糖尿病的当前方法:引入CRISPR/CAS9技术及非胚胎干细胞疗法的实例
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Human Induced Pluripotent Stem Cells in the Curative Treatment of Diabetes and Potential Impediments Ahead.人类诱导多能干细胞在糖尿病治疗中的应用及潜在障碍
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Current advanced therapy cell-based medicinal products for type-1-diabetes treatment.目前用于 1 型糖尿病治疗的先进治疗细胞基药物产品。
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The quest of cell surface markers for stem cell therapy.寻找用于干细胞治疗的细胞表面标志物。
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Applied as an MRI-Based Reporter Gene.应用于基于 MRI 的报告基因。
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CRISPR/Cas system: An emerging technology in stem cell research.CRISPR/Cas系统:干细胞研究中的一项新兴技术。
World J Stem Cells. 2019 Nov 26;11(11):937-956. doi: 10.4252/wjsc.v11.i11.937.

本文引用的文献

1
Efficient Generation and Editing of Feeder-free IPSCs from Human Pancreatic Cells Using the CRISPR-Cas9 System.利用CRISPR-Cas9系统从人胰腺细胞高效生成无饲养层诱导多能干细胞并进行编辑
J Vis Exp. 2017 Nov 8(129):56260. doi: 10.3791/56260.
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iPSC technology-based regenerative therapy for diabetes.基于 iPSC 技术的糖尿病再生疗法。
J Diabetes Investig. 2018 Mar;9(2):234-243. doi: 10.1111/jdi.12702. Epub 2017 Jul 29.
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The Application of CRISPR/Cas Technology to Efficiently Model Complex Cancer Genomes in Stem Cells.CRISPR/Cas 技术在干细胞中高效模拟复杂癌症基因组中的应用。
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Interspecies Chimerism with Mammalian Pluripotent Stem Cells.哺乳动物多能干细胞的种间嵌合体
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Interspecies organogenesis generates autologous functional islets.种间器官发生可产生自体功能性胰岛。
Nature. 2017 Feb 9;542(7640):191-196. doi: 10.1038/nature21070. Epub 2017 Jan 25.
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Directed differentiation of human iPSC into insulin producing cells is improved by induced expression of PDX1 and NKX6.1 factors in IPC progenitors.通过在胰岛祖细胞中诱导表达PDX1和NKX6.1因子,可改善人诱导多能干细胞向胰岛素产生细胞的定向分化。
J Transl Med. 2016 Dec 20;14(1):341. doi: 10.1186/s12967-016-1097-0.
7
Current stem cell based therapies in diabetes.当前基于干细胞的糖尿病治疗方法。
Am J Stem Cells. 2016 Oct 20;5(3):87-98. eCollection 2016.
8
Long-term immunosuppression after solitary islet transplantation is associated with preserved C-peptide secretion for more than a decade.孤立胰岛移植后的长期免疫抑制与长达十多年的C肽分泌保留有关。
Am J Transplant. 2015 Nov;15(11):2995-3001. doi: 10.1111/ajt.13383. Epub 2015 Jul 16.
9
C-peptide: new findings and therapeutic possibilities.C肽:新发现与治疗潜力
Diabetes Res Clin Pract. 2015 Mar;107(3):309-19. doi: 10.1016/j.diabres.2015.01.016. Epub 2015 Jan 21.
10
Tolerance induction and reversal of diabetes in mice transplanted with human embryonic stem cell-derived pancreatic endoderm.人胚胎干细胞源性胰腺内胚层移植诱导小鼠免疫耐受及逆转糖尿病
Cell Stem Cell. 2015 Feb 5;16(2):148-57. doi: 10.1016/j.stem.2014.12.001. Epub 2014 Dec 18.