Isolation and expansion of adult cardiac stem cells from human and murine heart

Isolation and expansion of adult cardiac stem cells from human and murine heart
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DOI:
10.1161/01.res.0000147315.71699.51
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发表时间:
2004-10-29
影响因子:
20.1
通讯作者:
Giacomello, A
Giacomello, A
中科院分区:
医学1区
文献类型:
--
作者:
Messina, E;De Angelis, L;Giacomello, A

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传统上认为心肌细胞是终末分化的细胞,其适应增加的工作并仅通过肥大来补偿疾病。然而,在过去的几年里,越来越多的令人信服的证据表明心脏具有再生潜力。最近的研究甚至推测存在驻留的心脏干细胞、通过细胞接触产生心肌细胞的内皮细胞或心肌细胞的心外祖细胞,但这些发现仍然存在争议。我们描述了未分化细胞的分离,生长为自我粘附集群(我们称之为“心球”)从出生后的心房或心室的人类活检标本和小鼠心脏的传代培养。这些细胞是克隆形成的,表达干细胞和内皮祖细胞抗原/标记物,并且似乎具有成体心脏干细胞的性质。它们能够长期自我更新,并可在体外和SCID米色小鼠异位(背侧皮下结缔组织)或原位(心肌梗死)移植后分化,产生心脏的主要特化细胞类型:肌细胞(即显示收缩活性和/或显示心肌细胞标志物的细胞)和血管细胞(即具有内皮或平滑肌标志物的细胞)。
Cardiac myocytes have been traditionally regarded as terminally differentiated cells that adapt to increased work and compensate for disease exclusively through hypertrophy. However, in the past few years, compelling evidence has accumulated suggesting that the heart has regenerative potential. Recent studies have even surmised the existence of resident cardiac stem cells, endothelial cells generating cardiomyocytes by cell contact or extracardiac progenitors for cardiomyocytes, but these findings are still controversial. We describe the isolation of undifferentiated cells that grow as self-adherent clusters (that we have termed "cardiospheres") from subcultures of postnatal atrial or ventricular human biopsy specimens and from murine hearts. These cells are clonogenic, express stem and endothelial progenitor cell antigens/markers, and appear to have the properties of adult cardiac stem cells. They are capable of long-term self-renewal and can differentiate in vitro and after ectopic (dorsal subcutaneous connective tissue) or orthotopic (myocardial infarction) transplantation in SCID beige mouse to yield the major specialized cell types of the heart: myocytes (ie, cells demonstrating contractile activity and/or showing cardiomyocyte markers) and vascular cells (ie, cells with endothelial or smooth muscle markers).