Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells
Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells
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DOI：
10.1172/jci12150
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发表时间：
2001-06-01
影响因子：
15.9
通讯作者：
Goodell, MA
中科院分区：
文献类型：
--
作者：
Jackson, KA;Majka, SM;Goodell, MA
在缺血损伤的哺乳动物心脏中，心肌细胞的丢失通常会导致不可逆转的心功能缺陷。为了确定能够修复受损心脏组织的干细胞来源，我们将高度浓缩的造血干细胞，即所谓的侧群(SP)细胞，移植到受到致死照射的小鼠体内，小鼠随后因冠状动脉闭塞60分钟而出现缺血，然后再灌流。移植的SP细胞(CD34(-)/low，c-Kit(+)，Sca-1(+))或其后代向缺血心肌和血管迁移，向心肌细胞和内皮细胞分化，促进功能组织的形成。从广泛表达1acZ的rosa26转基因小鼠中纯化了SP细胞。供体来源的心肌细胞主要分布在梗死区周围，发生率约为0.02%，通过LacZ和α-Actinin的表达以及CD45的缺失来鉴定。供体来源的内皮细胞通过LacZ和Flt-1的表达进行鉴定，Flt-1是SP细胞上缺失的内皮标记物。内皮植入的发生率约为3.3%，主要发生在梗塞附近的小血管。我们的结果证明了造血干细胞的心肌生成潜力，并提出了一种最终可能使心肌梗死患者受益的治疗策略。
Myocyte loss in the ischemically injured mammalian heart often leads to irreversible deficits in cardiac function. To identify a source of stem cells capable of restoring damaged cardiac tissue, we transplanted highly enriched hematopoietic stem cells, the so-called side population (SP) cells, into lethally irradiated mice subsequently rendered ischemic by coronary artery occlusion for 60 minutes followed by reperfusion. The engrafted SP cells (CD34(-)/low, c-Kit(+), Sca-1(+)) or their progeny migrated into ischemic cardiac muscle and blood vessels, differentiated to cardiomyocytes and endothelial cells, and contributed to the formation of functional tissue. SP cells were purified from Rosa26 transgenic mice, which express 1acZ widely. Donor-derived cardiomyocytes were found primarily in the peri-infarct region at a prevalence of around 0.02% and were identified by expression of lacZ and alpha -actinin, and lack of expression of CD45. Donor-derived endothelial cells were identified by expression of lacZ and Flt-1, an endothelial marker shown to be absent on SP cells. Endothelial engraftment was found at a prevalence of around 3.3%, primarily in small vessels adjacent to the infarct. Our results demonstrate the cardiomyogenic potential of hematopoietic stem cells and suggest a therapeutic strategy that eventually could benefit patients with myocardial infarction.