Early first trimester human embryonic cardiac Islet-1 progenitor cells and cardiomyocytes: Immunohistochemical and electrophysiological characterization
Early first trimester human embryonic cardiac Islet-1 progenitor cells and cardiomyocytes: Immunohistochemical and electrophysiological characterization
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DOI：
10.1016/j.scr.2009.10.001
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发表时间：
2010-01-01
影响因子：
1.2
通讯作者：
Grinnemo, Karl-Henrik
中科院分区：
文献类型：
--
作者：
Genead, Rami;Danielsson, Christian;Grinnemo, Karl-Henrik
本研究的目的是系统地研究早期人胚胎心脏中胰岛-1(+)(Isl1(+))祖细胞的分布、增殖和分化。在孕周5~10周的心脏中，发现Isl1(+)细胞，主要聚集在流出道内，少数聚集在心房和右室。其中一些簇也是肌钙蛋白T+。出乎意料的是，只有少数Isl1(+)细胞为Ki67(+)，而在脑室中，大多数Isl1(-)肌钙蛋白T(+)细胞为Ki67(+)。从消化的胚胎心脏衍生的培养物发展成自发跳动的心球。收获时心肌细胞肌钙蛋白T(+)和NKX2.5(+)表达频繁，白色Isl1仅在散在细胞中表达。仅有少数培养细胞表达Ki67。心球可以被冷冻、解冻，然后再培养成搏动的心球。在多电极阵列系统中，搏动的心球对肾上腺素能刺激有反应，并且表现出速率依赖的动作电位时程。总之，妊娠早期的人胚胎心脏表达Isl1(+)细胞团，其中一些分化为心肌细胞。出乎意料的是，只有一小部分Isl1(+)细胞在增殖，而大多数心肌细胞都是白色的。自发跳动的心球可以来自人类胚胎心脏，这些心球显示出功能的频率控制。(C)2009爱思唯尔B.V.保留所有权利。
The aims of this study were to systematically characterize the distribution, proliferation, and differentiation of Islet-1(+)(Isl1(+)) progenitor cells in the early first trimester human embryonic heart during which period most of the organogenesis takes place. In hearts of gestational week 5 to 10 Isl1(+) cells were identified and mainly clustered in the outflow tract and to a lesser extent in the atria and in the right ventricle. Some of the clusters were also troponin T+. Unexpectedly a only few Isl1(+) cells were Ki67(+) while in the ventricles a majority of Isl1(-)troponinT(+)cells were Ki67(+). Cultures derived from the digested embryonic heart developed into spontaneously beating cardiospheres. At harvest cells in these cardiospheres showed frequent expression of troponin T(+)and Nkx2.5(+), white Isl1 was expressed only in scattered cells. Only a minority of the cultured cells expressed Ki67. The cardiospheres could be frozen, thawed, and recultured to beating cardiospheres. In a multielectrode array system, the beating cardiospheres were responsive to adrenergic stimulation and exhibited rate-dependent action potential duration. In conclusion, the early first trimester human embryonic heart expresses clusters of Isl1(+)cells, some of which differentiate into cardiomyocytes. Unexpectedly, only a minority of the Isl1(+)cells, white a majority of ventricular cardiomyocytes, were proliferating. Spontaneously beating cardiospheres could be derived from the human embryonic heart and these cardiospheres showed functional frequency control. (C) 2009 Elsevier B.V. All rights reserved.