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诱导多能干细胞的临床应用 - 现状。

Clinical Applications of Induced Pluripotent Stem Cells - Stato Attuale.

机构信息

Department of Genetic Engineering, SRM Institute of Science and Technology, Chennai, India.

出版信息

Adv Exp Med Biol. 2018;1079:127-149. doi: 10.1007/5584_2018_173.

Abstract

In an adult human body, somatic stem cells are present in small amounts in almost all organs with the function of general maintenance and prevention of premature aging. But, these stem cells are not pluripotent and are unable to regenerate large cellular loss caused by infarctions or fractures especially in cells with limited replicative ability such as neurons and cardiomyocytes. These limitations gave rise to the idea of inducing pluripotency to adult somatic cells and thereby restoring their regeneration, replication and plasticity. Though many trials and research were focused on inducing pluripotency, a solid breakthrough was achieved by Yamanaka in 2006. Yamanaka's research identified 4 genes (OCT-4, SOX-2, KLF-4 and c-MYC) as the key requisite for inducing pluripotency in any somatic cells (iPSCs). Our study, reviews the major methods used for inducing pluripotency, differentiation into specific cell types and their application in both cell regeneration and disease modelling. We have also highlighted the current status of iPSCs in clinical applications by analysing the registered clinical trials. We believe that this review will assist the researchers to decide the parameters such as induction method and focus their efforts towards clinical application of iPSCs.

摘要

在成年人的体内,体干细胞存在于几乎所有具有一般维持和预防过早衰老功能的器官中,但数量很少。但是,这些干细胞不是多能的,无法再生由梗死或骨折引起的大量细胞损失,特别是在具有有限复制能力的细胞中,如神经元和心肌细胞。这些局限性促使人们产生了诱导成体体细胞多能性的想法,从而恢复其再生、复制和可塑性。尽管许多试验和研究都集中在诱导多能性上,但 2006 年,Yamanaka 取得了坚实的突破。Yamanaka 的研究确定了 4 个基因(OCT-4、SOX-2、KLF-4 和 c-MYC)是诱导任何体体细胞多能性的关键必需基因(iPS 细胞)。我们的研究综述了诱导多能性、分化为特定细胞类型及其在细胞再生和疾病建模中的应用的主要方法。我们还通过分析已注册的临床试验,强调了 iPS 细胞在临床应用中的现状。我们相信,这篇综述将帮助研究人员决定诸如诱导方法等参数,并将努力集中在 iPS 细胞的临床应用上。

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