Human progenitor cells derived from cardiac adipose tissue ameliorate myocardial infarction in rodents
Human progenitor cells derived from cardiac adipose tissue ameliorate myocardial infarction in rodents
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DOI：
10.1016/j.yjmcc.2010.08.010
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发表时间：
2010-11-01
影响因子：
5
通讯作者：
Izpisua Belmonte, Juan Carlos
中科院分区：
文献类型：
--
作者：
Bayes-Genis, Antoni;Soler-Botija, Carolina;Izpisua Belmonte, Juan Carlos
血管闭塞引起的心肌梗死会导致无功能纤维组织的形成。累积的证据表明，细胞疗法可以适度改善心脏功能；因此，人们积极寻找具有修复受损组织潜力的新细胞来源。在这里，我们从成人心脏脂肪组织的活检组织中鉴定和表征了心脏脂肪组织衍生的祖细胞(ATDPC)的细胞群。心脏ATDPC表达间充质干细胞样标记物(CD105、CD44、CD166、CD29和CD90强阳性)，具有免疫抑制能力。此外，心脏ATDPC具有固有的心脏样表型，能够在体外表达新陈代谢的心肌和内皮标志物，但不能分化为脂肪细胞。此外，在小鼠和大鼠心肌梗死模型中，将ATDPC移植到损伤的心肌中，移植的细胞表达心脏(肌钙蛋白I、肌小球α-肌动蛋白)和内皮(CD31)标志物，血管形成增加，梗死面积缩小。此外，对照组和细胞处理组之间的短轴缩短率和射血分数有显著差异，在心脏植入ATDPC后30天，前壁仍然显著增厚。最后，在体外低氧条件下，心脏ATDPC分泌促血管生成因子，提示旁分泌效应促进局部血管形成。我们的结果表明，从人心脏脂肪组织中分离的祖细胞群体可能是未来用于再生受损心肌的细胞治疗的有效候选细胞。(C)2010爱思唯尔有限公司。保留所有权利。
Myocardial infarction caused by vascular occlusion results in the formation of nonfunctional fibrous tissue. Cumulative evidence indicates that cell therapy modestly improves cardiac function; thus, novel cell sources with the potential to repair injured tissue are actively sought. Here, we identify and characterize a cell population of cardiac adipose tissue-derived progenitor cells (ATDPCs) from biopsies of human adult cardiac adipose tissue. Cardiac ATDPCs express a mesenchymal stem cell-like marker profile (strongly positive for CD105, CD44, CD166, CD29 and CD90) and have immunosuppressive capacity. Moreover, cardiac ATDPCs have an inherent cardiac-like phenotype and were able to express de nova myocardial and endothelial markers in vitro but not to differentiate into adipocytes. In addition, when cardiac ATDPCs were transplanted into injured myocardium in mouse and rat models of myocardial infarction, the engrafted cells expressed cardiac (troponin I, sarcomeric alpha-actinin) and endothelial (CD31) markers, vascularization increased, and infarct size was reduced in mice and rats. Moreover, significant differences between control and cell-treated groups were found in fractional shortening and ejection fraction, and the anterior wall remained significantly thicker 30 days after cardiac delivery of ATDPCs. Finally, cardiac ATDPCs secreted proangiogenic factors under in vitro hypoxic conditions, suggesting a paracrine effect to promote local vascularization. Our results indicate that the population of progenitor cells isolated from human cardiac adipose tissue (cardiac ATDPCs) may be valid candidates for future use in cell therapy to regenerate injured myocardium. (C) 2010 Elsevier Ltd. All rights reserved.