Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts
Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts
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DOI：
10.1038/nature02446
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发表时间：
2004-04-08
期刊：
影响因子：
64.8
通讯作者：
Field, LJ
中科院分区：
文献类型：
--
作者：
Murry, CE;Soonpaa, MH;Field, LJ
哺乳动物的心脏具有非常有限的再生能力，因此通过瘢痕形成愈合（1）。最近的报告表明，造血干细胞可以转分化成意想不到的表型，如骨骼肌（2，3），肝细胞（4），上皮细胞（5），神经元（6，7），内皮细胞（8）和心肌细胞（8，9），在组织损伤或放置在一个新的环境。此外，移植的人心脏含有来源于心脏外祖细胞的肌细胞（10-12），其可能来源于骨髓（8，13 -15）。尽管大多数研究表明，转分化在生理条件下是极其罕见的，但最近报道了直接干细胞注射后心肌梗死的广泛再生（9），促进了几项临床试验（16，17）。在这里，我们使用心肌细胞限制性和普遍表达的报告转基因来追踪145个移植到正常和受伤的成年小鼠心脏后造血干细胞的命运。当使用这些遗传技术追踪细胞命运时，没有检测到向心肌细胞的转分化，与假移植心脏相比，干细胞移植心脏显示心肌细胞没有明显增加。这些结果表明，造血干细胞不容易获得心脏表型，并提出了一个警示说明梗死修复的临床研究。
The mammalian heart has a very limited regenerative capacity and, hence, heals by scar formation(1). Recent reports suggest that haematopoietic stem cells can transdifferentiate into unexpected phenotypes such as skeletal muscle(2,3), hepatocytes(4), epithelial cells(5), neurons(6,7), endothelial cells(8) and cardiomyocytes(8,9), in response to tissue injury or placement in a new environment. Furthermore, transplanted human hearts contain myocytes derived from extra-cardiac progenitor cells(10-12), which may have originated from bone marrow(8,13-15). Although most studies suggest that transdifferentiation is extremely rare under physiological conditions, extensive regeneration of myocardial infarcts was reported recently after direct stem cell injection(9), prompting several clinical trials(16,17). Here, we used both cardiomyocyte-restricted and ubiquitously expressed reporter transgenes to track the fate of haematopoietic stem cells after 145 transplants into normal and injured adult mouse hearts. No transdifferentiation into cardiomyocytes was detectable when using these genetic techniques to follow cell fate, and stem-cell-engrafted hearts showed no overt increase in cardiomyocytes compared to sham-engrafted hearts. These results indicate that haematopoietic stem cells do not readily acquire a cardiac phenotype, and raise a cautionary note for clinical studies of infarct repair.