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诱导多能干细胞在心血管生物学中的应用:表观遗传学、前景与挑战。

Induced pluripotent cells in cardiovascular biology: epigenetics, promises, and challenges.

机构信息

Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.

出版信息

Prog Mol Biol Transl Sci. 2012;111:27-49. doi: 10.1016/B978-0-12-398459-3.00002-2.

Abstract

Cardiovascular diseases are still the leading cause of death worldwide. Despite the improvement shown in the prognosis of patients with acute MI, there remains still a significant mortality risk. Since the main underlying problem after an MI is the loss of cardiomyocytes and microvasculature, treatment strategies aimed at preserving or regenerating myocardial tissue have been examined as potential therapeutic modalities. Toward this goal, many cell types are being investigated as potent sources of cardiomyocytes for cell transplantation. The progress made toward the generation of induced Pluripotent Stem (iPS) cells hold great potential for future use in myocardial repair. We review critical aspects of these cell's potential, such as their generation, their differentiating ability, the known epigenetic mechanisms that allow for their reprogramming, maintenance of pluripotency, their cardiovascular differentiation and therapeutic potential, and the possibility of an epigenetic memory. Understanding the molecular circuitry of these cells will provide a better understanding of their potential as well as limitations in future clinical use.

摘要

心血管疾病仍然是全球范围内的主要死亡原因。尽管急性心肌梗死(MI)患者的预后有所改善,但仍存在显著的死亡风险。由于 MI 后主要的潜在问题是心肌细胞和微血管的丧失,因此人们一直在研究旨在保存或再生心肌组织的治疗策略,作为潜在的治疗方法。为此,许多细胞类型被作为细胞移植的潜在心肌细胞来源进行了研究。在诱导多能干细胞(iPS)的生成方面取得的进展为未来心肌修复的应用提供了巨大的潜力。我们回顾了这些细胞的潜在关键方面,如它们的生成、分化能力、允许其重编程的已知表观遗传机制、多能性的维持、它们的心血管分化和治疗潜力,以及表观遗传记忆的可能性。了解这些细胞的分子电路将更好地理解它们在未来临床应用中的潜力和局限性。

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