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用于缺血性心脏病的干细胞疗法:我们进展到哪一步了?

Stem cell therapy for ischemic heart disease: where are we?

作者信息

LaPar Damien J, Kron Irving L, Yang Zequan

机构信息

Department of Surgery, University of Virginia, Charlottesville, Virginia, USA.

出版信息

Curr Opin Organ Transplant. 2009 Feb;14(1):79-84. doi: 10.1097/MOT.0b013e328320d2e2.

Abstract

PURPOSE OF REVIEW

Stem cell transplantation is currently generating a great deal of interest in the treatment of ischemic heart disease (IHD) as the replacement of akinetic scar tissue by viable myocardium should improve cardiac function, impede progressive left ventricular remodeling, and revascularize ischemic areas. Substantial work in stem cell therapy for ischemic heart disease has recently been reported.

RECENT FINDINGS

Stem cell populations have been expanding. Most recently, induced pluripotent stem (iPS) cells have been discovered that have the potential to revolutionize stem cell therapy. Many of the efforts in stem cell therapy for ischemic heart disease have been inconclusive and often contradicting. Transdifferentiation of stem cells into cardiomyocytes remains controversial. The therapeutic effect of the stem cell seems consistent with paracrine function rather than transdifferentiation. Systemic and micromilieu factors appear to dictate the fate of implanted stem cells.

SUMMARY

Although animal studies produce controversial results, and many basic questions remain unanswered, more and more clinical trials are underway. Consequently, researchers must begin to focus upon a few basic critical issues: the modulation of the systemic and microenvironment for stem cells in order to augment stem cell survival and transdifferentiation; the underlying mechanisms of stem cell therapy and the fate of stem cells; differentiation into myocytes or other terminal cell populations with favorable paracrine functions.

摘要

综述目的

目前,干细胞移植在缺血性心脏病(IHD)治疗中引起了广泛关注,因为用有活力的心肌替代无运动功能的瘢痕组织有望改善心脏功能、阻止左心室进行性重塑并使缺血区域血管再生。最近已有大量关于缺血性心脏病干细胞治疗的研究报道。

最新发现

干细胞群体不断扩大。最近发现的诱导多能干细胞(iPS细胞)有可能彻底改变干细胞治疗。缺血性心脏病干细胞治疗的许多研究结果尚无定论,且常常相互矛盾。干细胞向心肌细胞的转分化仍存在争议。干细胞的治疗效果似乎与旁分泌功能而非转分化一致。全身和微环境因素似乎决定了植入干细胞的命运。

总结

尽管动物研究结果存在争议,许多基本问题仍未得到解答,但越来越多的临床试验正在进行。因此,研究人员必须开始关注一些基本的关键问题:调节干细胞的全身和微环境以提高干细胞存活率和转分化能力;干细胞治疗的潜在机制以及干细胞的命运;分化为具有良好旁分泌功能的心肌细胞或其他终末细胞群体。

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