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A Concise Review on Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Personalized Regenerative Medicine
Stem Cell Reviews and Reports ( IF 4.8 ) Pub Date : 2020-10-23 , DOI: 10.1007/s12015-020-10061-2
Pallavi Pushp 1, 2 , Diogo E S Nogueira 3 , Carlos A V Rodrigues 3 , Frederico C Ferreira 3 , Joaquim M S Cabral 3 , Mukesh Kumar Gupta 2
Affiliation  

The induced pluripotent stem cells (iPSCs) are derived from somatic cells by using reprogramming factors such as Oct4, Sox2, Klf4, and c-Myc (OSKM) or Oct4, Sox2, Nanog and Lin28 (OSNL). They resemble embryonic stem cells (ESCs) and have the ability to differentiate into cell lineage of all three germ-layer, including cardiomyocytes (CMs). The CMs can be generated from iPSCs by inducing embryoid bodies (EBs) formation and treatment with activin A, bone morphogenic protein 4 (BMP4), and inhibitors of Wnt signaling. However, these iPSC-derived CMs are a heterogeneous population of cells and require purification and maturation to mimic the in vivo CMs. The matured CMs can be used for various therapeutic purposes in regenerative medicine by cardiomyoplasty or through the development of tissue-engineered cardiac patches. In recent years, significant advancements have been made in the isolation of iPSC and their differentiation, purification, and maturation into clinically usable CMs. Newer small molecules have also been identified to substitute the reprogramming factors for iPSC generation as well as for direct differentiation of somatic cells into CMs without an intermediary pluripotent state. This review provides a concise update on the generation of iPSC-derived CMs and their application in personalized cardiac regenerative medicine. It also discusses the current limitations and challenges in the application of iPSC-derived CMs.



中文翻译:

用于个性化再生医学的诱导多能干细胞衍生心肌细胞简述

诱导多能干细胞 (iPSC) 通过使用重编程因子如 Oct4、Sox2、Klf4 和 c-Myc (OSKM) 或 Oct4、Sox2、Nanog 和 Lin28 (OSNL) 从体细胞衍生而来。它们类似于胚胎干细胞 (ESC),并能够分化成所有三个胚层的细胞谱系,包括心肌细胞 (CM)。通过诱导胚状体 (EB) 形成和用激活素 A、骨形态发生蛋白 4 (BMP4) 和 Wnt 信号传导抑制剂处理,可以从 iPSC 生成 CM。然而,这些 iPSC 衍生的 CM 是异质的细胞群,需要纯化和成熟来模拟体内 CM。成熟的 CM 可通过心肌成形术或通过组织工程心脏补片的开发用于再生医学中的各种治疗目的。最近几年,在 iPSC 的分离及其分化、纯化和成熟为临床可用 CM 方面取得了重大进展。新的小分子也已被鉴定用于替代 iPSC 生成的重编程因子,以及将体细胞直接分化为没有中间多能状态的 CM。本综述简要介绍了 iPSC 衍生 CM 的生成及其在个性化心脏再生医学中的应用。它还讨论了当前应用 iPSC 衍生 CM 的局限性和挑战。新的小分子也已被鉴定用于替代 iPSC 生成的重编程因子,以及将体细胞直接分化为没有中间多能状态的 CM。本综述简要介绍了 iPSC 衍生 CM 的生成及其在个性化心脏再生医学中的应用。它还讨论了当前应用 iPSC 衍生 CM 的局限性和挑战。新的小分子也已被鉴定用于替代 iPSC 生成的重编程因子,以及将体细胞直接分化为没有中间多能状态的 CM。本综述简要介绍了 iPSC 衍生 CM 的生成及其在个性化心脏再生医学中的应用。它还讨论了当前应用 iPSC 衍生 CM 的局限性和挑战。

更新日期:2020-10-30
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