Adult bone marrow-derived cells do not acquire functional attributes of cardiomyocytes when transplanted into peri-infarct myocardium
Adult bone marrow-derived cells do not acquire functional attributes of cardiomyocytes when transplanted into peri-infarct myocardium
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DOI：
10.1038/mt.2008.64
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发表时间：
2008-06-01
影响因子：
12.4
通讯作者：
Rubart, Michael
中科院分区：
文献类型：
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作者：
Scherschel, John A.;Soonpaa, Mark H.;Rubart, Michael
成人骨髓(BM)细胞直接移植到缺血损伤的心脏中后的心肌生成潜力仍然是一个有争议的问题。在这项研究中，我们研究了移植的骨髓细胞在原位膜去极化时产生细胞内钙瞬变([Ca~(2+)](I))的能力。从普遍表达增强型绿色荧光蛋白(EGFP)的成年转基因小鼠中获得低密度单核(LDM)BM细胞、c-kit(Enr)富集型(c-kit(Enr))BM细胞和高度浓缩的LIN(-)c-kit(+)BM细胞，并将其注射到非转基因小鼠的梗死灶周围心肌。9-10天后处死小鼠，取出心脏，以朗宁多夫模式灌流，负载钙敏感的荧光载体Rhod-2，并在双光子激光扫描荧光显微镜(TPLSM)下监测表达EGFP的供体来源细胞和非表达的宿主心肌细胞的动作电位诱导的[Ca+](I)瞬变。虽然在移植物-宿主交界处和远离梗塞区的宿主心肌细胞中发现自发的和电诱发的[Ca~(2+)](I)瞬变同步发生，但它们在所有>；3000个成簇的骨髓来源细胞中都不存在，这些细胞分布在整个梗死区瘢痕或梗死区周围。我们得出结论，移植的BM来源的细胞缺乏功能心肌细胞的属性，这对成年BM细胞可以在梗塞心脏内引起实质性的心肌细胞再生的概念提出了质疑。
The cardiomyogenic potential of adult bone marrow ( BM) cells after being directly transplanted into the ischemically injured heart remains a controversial issue. In this study, we investigated the ability of transplanted BM cells to develop intracellular calcium ([Ca2+](i)) transients in response to membrane depolarization in situ. Low-density mononuclear ( LDM) BM cells, c-kit-enriched ( c-kit(enr)) BM cells, and highly enriched lin(-)c-kit(+) BM cells were obtained from adult transgenic mice ubiquitously expressing enhanced green fluorescent protein ( EGFP), and injected into peri-infarct myocardiums of nontransgenic mice. After 9-10 days the mice were killed, and the hearts were removed, perfused in Langendorff mode, loaded with the calcium-sensitive fluorophore rhod-2, and subjected to two-photon laser scanning fluorescence microscopy ( TPLSM) to monitor action potential-induced [Ca2+](i) transients in EGFP-expressing donor-derived cells and non-expressing host cardiomyocytes. Whereas spontaneous and electrically evoked [Ca2+](i) transients were found to occur synchronously in host cardiomyocytes along the graft-host border and in areas remote from the infarct, they were absent in all of the > 3,000 imaged BM-derived cells that were located in clusters throughout the infarct scar or peri-infarct zone. We conclude that engrafted BM-derived cells lack attributes of functioning cardiomyocytes, calling into question the concept that adult BM cells can give rise to substantive cardiomyocyte regeneration within the infarcted heart.