“在我的眼与心之间有一个联盟被建立”:基于诱导多能干细胞的肌营养不良相关心肌病模型的进展。

"Betwixt Mine Eye and Heart a League Is Took": The Progress of Induced Pluripotent Stem-Cell-Based Models of Dystrophin-Associated Cardiomyopathy.

机构信息

Centro Cardiologico Monzino-IRCCS, Unit of Vascular Biology and Regenerative Medicine, 20138 Milan, Italy.

Centro Cardiologico Monzino-IRCCS, Department of Cardiac Surgery, Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy.

出版信息

Int J Mol Sci. 2020 Sep 23;21(19):6997. doi: 10.3390/ijms21196997.

Abstract

The ultimate goal of precision disease modeling is to artificially recreate the disease of affected people in a highly controllable and adaptable external environment. This field has rapidly advanced which is evident from the application of patient-specific pluripotent stem-cell-derived precision therapies in numerous clinical trials aimed at a diverse set of diseases such as macular degeneration, heart disease, spinal cord injury, graft-versus-host disease, and muscular dystrophy. Despite the existence of semi-adequate treatments for tempering skeletal muscle degeneration in dystrophic patients, nonischemic cardiomyopathy remains one of the primary causes of death. Therefore, cardiovascular cells derived from muscular dystrophy patients' induced pluripotent stem cells are well suited to mimic dystrophin-associated cardiomyopathy and hold great promise for the development of future fully effective therapies. The purpose of this article is to convey the realities of employing precision disease models of dystrophin-associated cardiomyopathy. This is achieved by discussing, as suggested in the title echoing William Shakespeare's words, the settlements (or "leagues") made by researchers to manage the constraints ("betwixt mine eye and heart") distancing them from achieving a perfect precision disease model.

摘要

精准疾病建模的最终目标是在外在环境中人为地重现受影响人群的疾病。该领域取得了飞速发展,从众多旨在治疗多种疾病(如黄斑变性、心脏病、脊髓损伤、移植物抗宿主病和肌肉萎缩症)的临床试验中,应用患者特异性多能干细胞衍生的精准疗法可见一斑。尽管存在一些半有效的方法来缓解肌营养不良症患者的骨骼肌退化,但非缺血性心肌病仍然是主要死亡原因之一。因此,源自肌营养不良症患者诱导多能干细胞的心血管细胞非常适合模拟肌营养不良相关的心肌病,为未来开发完全有效的疗法提供了巨大的希望。本文的目的是传达使用肌营养不良相关心肌病精准疾病模型的现实情况。通过讨论,正如标题所暗示的那样,回应威廉·莎士比亚的话,研究人员为了克服实现完美精准疾病模型的限制而做出的“妥协”(或“联盟”)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1a2/7582534/0edeb879722a/ijms-21-06997-g001.jpg

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