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摘要
心血管疾病和相关疾病任然是世界上导致死亡的主要原因。由于患病心脏再生非常有限,并且供体器官的供应十分不足,所以,我们只有寄希望用于心脏修复的新方法。恢复内源性心肌细胞的增殖或者将成人干细胞移植入心脏很难成功治疗心血管疾病。因此,科学家正在研究从体外产生心肌样细胞(CMs)以补充损失的功能性心肌组织。该方法需要有可持续的CMs来源。诱导性多潜能干细胞(iPSC)为发展自体细胞治疗提供了希望。为了产生用于心脏修复的CMs,我们需要诱导分化得到安全有效的iPSC。近年来,通过异位表达心脏转录因子或补充化学途径调节剂,IPSC分化为CMS细胞甚至功能亚型已经实现。另一种方法是将成纤维细胞转分化成谱系特异性细胞,这存在于许多器官的间质组织中。通过特异性转录因子组合的异位表达来诱导心肌样细胞的形成(ICMS)已被证明存在于体内外。IPSC诱导中间状态可有可无,这是一个很重要的研究理念。然而,大多数早期实验以小鼠为模型,转换成相对大型的动物模型或者进行临床是一项极具挑战的工作。本文对该领域的进展、缺点和前景进行了讨论。
关键词: 心肌细胞,诱导多能干细胞,重编程,转分化,诱导的心肌细胞,心肌转录因子。
Current Gene Therapy
Title:Directing Cardiomyogenic Differentiation and Transdifferentiation By Ectopic Gene Expression – Direct Transition Or Reprogramming Detour?
Volume: 16 Issue: 1
Author(s): Birgit Andrée and Robert Zweigerdt
Affiliation:
关键词: 心肌细胞,诱导多能干细胞,重编程,转分化,诱导的心肌细胞,心肌转录因子。
摘要: Cardiovascular disorders and associated morbidities remain the leading cause of premature death worldwide. Since the regeneration of diseased hearts is very limited and the insufficient supply of donor organs persists, hopes rely on new therapies for heart repair. Reviving the proliferation of endogenous cardiomyocytes (CMs) or the administration of adult stem cells to the heart was of limited curative success to date. Thus, the administration of in vitro generated CMs is under investigation to replenish loss of functional heart muscle tissue. This requires a sustainable source of CMs. Induced pluripotent stem cells (iPSC) have raised hopes for developing autologous cell therapies. To serve for heart repair, efficient and safe iPSC differentiation protocols for CMs production are required. iPSC differentiation into CMs and even functional subtypes was indeed achieved in recent years, either by the ectopic expression of cardiac transcription factors or the supplementation of chemical pathway modulators. An alternative approach aims at the direct transdifferentiation of fibroblasts, which are present in the interstitial tissue of many organs, into functional lineage-specific cell types. As a result the formation of induced cardiomyocyte-like cells (iCMs) by the ectopic expression of specific transcription factors combinations has been demonstrated in vitro and in vivo. This is an important proof-of-concept that the intermediate state of iPSC induction is dispensable. However, most of the early experiments were conducted in mice and translation to more relevant large animal models and subsequently to the clinic are challenging. Progress, drawbacks, and perspectives in this field will be discussed.
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Birgit Andrée and Robert Zweigerdt , Directing Cardiomyogenic Differentiation and Transdifferentiation By Ectopic Gene Expression – Direct Transition Or Reprogramming Detour?, Current Gene Therapy 2016; 16 (1) . https://dx.doi.org/10.2174/1566523216666160104141522
DOI https://dx.doi.org/10.2174/1566523216666160104141522 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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