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干细胞移植治疗缺血性心脏病的进展及其作用机制

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高连如

解放军海军总医院心内科,北京市100037

中国组织工程研究与临床康复
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国际标准刊号:ISSN 1673-8225
国内统一刊号:CN 11-5516/R

摘  要:

学术背景:心肌梗死后,尽管现有的内外科治疗手段可以改善冠状动脉供血、挽救缺血心肌,但对已坏死的心肌或无功能心肌尚无良好治疗措施。细胞作为构成心脏结构、执行心脏功能的物质基础,尽管存在争议,但大量研究资料表明干细胞移植治疗是安全有效的。 目的:文章试图就目前成体干细胞在缺血,陛心脏病治疗的临床研究进展做一综述,客观评价成体干细胞治疗缺血性心脏病的安全性、有效性,阐述成体干细胞改善心功能的可能机制,介绍当今临床研究方向。 检索策略:由该论文的研究人员应用计算机检索Pubmed数据库1996/2007成体干细胞与缺血性心脏病方面的文献,检索词“adult stem cells,ischemial heart disease,cardiomyocytes”,并限定文章语言种类为English。同时计算机检索中国期刊全文数据库1996/2007的相关文献,检索词“成年干细胞,心肌细胞,缺血性心脏病”,并限定文章语言种类为中文。共检索到1303篇文献,对资料进行初审,纳入标准:①文章所述内容应与缺血性心脏病干细胞移植密切相关。②同一领域选择近期发表或在权威杂志上发表的文章。排除标准:①重复性研究。②Meta分析。 文献评价:文献的来源主要是通过对干细胞移植治疗缺血,陛心脏病现状及其作用机制进行汇总分析。1303篇文献中,动物实验和在体、离体、细胞学实验626篇,综述、述评、讲座类文献345篇,临床研究45篇,选用其中的46篇作为本文参考文献。 资料综合:①干细胞为一群具有自我更新、多向分化潜能的原始细胞,分为胚胎干细胞和成体干细胞。虽然研究表明胚胎干细胞较成体干细胞具有更强的增殖和分化潜能,但由于其涉及伦理道德、来源困难等原因,限制了它的使用。②就目前已完成的包括不同类型的成体细胞(如骨髓单个核细胞、内皮祖细胞、CD133^+细胞、骨髓间充质干细胞、成肌细胞等)移植治疗缺血性心脏病的早期临床试验来看,尽管存在样本小、缺乏随机对照等不足,但均显示一个公认的事实,即无论采用何种方法移植成体干细胞治疗缺血性心脏病均是安全有效的。这对于正在进行的较大规模的临床研究是十分重要的,为其提供了更充分的临床资料。③多数研究认为干细胞改善心功能的作用机制包括直接与间接效应,如移植细胞横向分化为再生心肌与血管、移植细胞的旁分泌作用促进血管再生、抑制心肌细胞凋亡及心室重构等。近来研究认为外源前体移植心肌可以刺激机体内源心肌存留的干细胞增殖,从而改善心功能。 结论:尽管目前成体干细胞改善心功能的确切机制仍不清楚,但多数早期临床研究表明成体干细胞移植治疗缺血性心脏病是安全有效的。当前的研究方向是需要随机、双盲、安慰剂对照的多中心临床试验。[著者文摘]

303篇文献中,动物实验和在体、离体、细胞学实验626篇,综述、述评、讲座类文献345篇,临床研究45篇,选用其中的46篇作为本文参考文献。资料综合:①干细胞为一群具有自我更新、多向分化潜能的原始细胞,分为胚胎干细胞和成体干细胞。虽然研究表明胚胎干细胞较成体干细胞具有更强的增殖和分化潜能,但由于其涉及伦理道德、来源困难等原因,限制了它的使用。②就目前已完成的包括不同类型的成体细胞(如骨髓单个核细胞、内皮祖细胞、CD133 细胞、骨髓问充质干细胞、成肌细胞等)移植治疗缺血性心脏病的早期临床试验来看,尽管存在样本小、缺乏随机对照等不足,但均显示一个公认的事实,即无论采用何种方法移植成体干细胞治疗缺血性心脏病均是安全有效的。这对于正在进行的较大规模的临床研究是十分重要的,为其提供了更充分的临床资料。③多数研究认为干细胞改善心功能的作用机制包括直接与间接效应,如移植细胞横向分化为再生心肌与血管、移植细胞的旁分泌作用促进血管再生、抑制心肌细胞凋亡及心室重构等......

栏目信息:

综述与专论

分 类 号:

R394.2

文献标识码:

A

文章编号:

1673-8225(2007)46-09346-07

相关文章:

参考文献(46篇) 耦合文献(16篇)  主题相关

[参考文献]

Progress and mechanism of stem cell transplantation in the treatment of ischemic heart disease

Gao LR.( Department of Cardiology, Naval General Hospital of Chinese PLA, Beijing 100037, China)

Abstract:

BACKGROUND: Despite the advanced therapeutic strategies of medical intervention and surgical procedures after myocardial infarction, which may improve coronary blood flow and salvage ischemic myocardium, is still not able to salvage necrosis or non-functional myocardium. Stem cells, as the material foundation of heart structures and function, have been proved to be one of safe and effective therapies for the improvement of cardiac function, although it is still extremely controversial. OBJECTIVE; To summarize the clinical research progress on adult stem cells in treatment of ischemic heart disease, evaluate the safety and efficacy of adult stem cell therapy, speculate the mechanisms of adult stem calls on improving heart function, and introduce the future clinical study of adult stem calls. RETRIEVE STRATEGY: English articles of adult stem cells and ischemic heart disease were searched in Pubmed databases published from 1996 to 2007, with the key words "adult stem cells, cardiomyocytes, ischemic heart disease". Meanwhile, a computer-based search was conducted in China Journal Full-text Database with the key words of "adult stem cell, cardiomyocytes, ischemic heart disease" between 1996 and 2007. Total 1 303 articles were selected firstly. Inclusive criteria: ①The literatures were closely related to adult stem cell and ischemic heart disease.②The literatures of the same field were selected by the recent publication or the authority magazine publication. Exclusive criteria: repetitive researches.③Meta analysis. LITERATURE EVALUATION: The selected articles were mainly the reviews of the current status and mechanism of stem cell transplantation for ischemic heart disease. There were 626 out of the selected 1 303 articles referring to the animal experiments and in vivo, in vitro, cytological trials, 345 ones were the reviews, statements and reports, remaining 45 were clinical researches. Finally 46 articles were selected for the references. DATA SYNTHESIS: ①Stem cell defining characteristics is the capacity to differentiate into a spectrum of different cell types and renew themselves, which is divided into embryonic stem cells and adult stem cells. Although embryonic stem cells have been shown to have greater potency for proliferation and differentiation than adult stem cells, their lack of availability and ethical issues hamper clinical applications. ②At present, a number of early clinical studies have been published, despite most of the them are small pilot studies that even lack randomization or control groups, the fact that several cell types (including bone marrow mononuclear cells, endothelial progenitor calls, CD133+ cells, mesenchymal stem cells, skeletal myoblasts), have been studied using different delivery methods, the overwhelming message from all of these studies is that cell therapy is safe and feasible for ischemic heart disease. In addition, the results of these studies provide the clinical data for the ongoing studies.③Adult stem cells may improve cardiac function by various potential mechanisms, including direct or indirect effects. Differentiation into cardiomyocytes may contribute to cardiac regeneration. Paracnne factors released by progenitor cells may inhibit cardiac apoptosis, affect remodeling, or enhance neovascualrization. New data show that exogenous stem cells may stimulate proliferation of endogenous cardiac precursors. CONCLUSION: At present, despite the action mechanisms of adult stem cells on the functional improvement of heart after myocardial infarction remain unclear, there is a wealth of early clinical data showing safety, feasibility and early efficacy of adult stem cell therapy for ischemic heart disease. Adult stem cell therapies should proceed into randomized, placebo-controlled and double-blind multicenter clinical trials.[著者文摘]

收稿日期: 2007-07-16
修订日期: 2007-09-13

基金资助:

国家“八六三”计划(2006AA022469)

作者简介:

高连如,女,解放军第二军医大学毕业,1996~2000年美国加利福尼亚大学旧金山,0血管研究所博士后研究员,主任医师、主要从事心血管介入与干细胞治疗方面的研究。lianru@yahoo.com.cn

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