A purified population of multipotent cardiovascular progenitors derived from primate pluripotent stem cells engrafts in postmyocardial infarcted nonhuman primates
A purified population of multipotent cardiovascular progenitors derived from primate pluripotent stem cells engrafts in postmyocardial infarcted nonhuman primates
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DOI：
10.1172/jci40120
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发表时间：
2010-04-01
影响因子：
15.9
通讯作者：
Puceat, Michel
中科院分区：
文献类型：
--
作者：
Blin, Guillaume;Nury, David;Puceat, Michel
细胞疗法有望实现组织再生，包括晚期心力衰竭患者。然而，用骨髓细胞和骨骼肌祖细胞治疗心脏病在临床试验中只有边际积极效益，可能是因为成体干细胞的可塑性有限。在人类多能干细胞中鉴定出第一个心脏谱系发育所需的早期心血管祖细胞，将为人类心脏发生提供线索，并可能为心脏退行性疾病的细胞治疗铺平道路。在这里，我们报告了心血管祖细胞的早期群体的分离，其特征在于OCT 4，阶段特异性胚胎抗原1（SSEA-1）和中胚层后1（MESP 1）的表达，来自于用心源性形态发生蛋白BMP 2处理的人多能干细胞。这种祖细胞群是多能的，能够产生心肌细胞以及平滑肌和内皮细胞。当移植到免疫抑制的非人灵长类动物的梗死心肌中时，来自恒河猴胚胎干细胞的SSEA-1（+）祖细胞群分化为心室肌细胞，并重建了20%的瘢痕组织。值得注意的是，移植了未纯化的心脏定向细胞群（包括SSEA-1（-）细胞）的灵长类动物在疤痕组织中产生了畸胎瘤，而移植了纯化的SSEA-1（+）细胞的灵长类动物则没有。因此，我们相信，我们在这里描述的SSEA-1（+）祖细胞有潜力用于心脏再生医学。
Cell therapy holds promise for tissue regeneration, including in individuals with advanced heart failure. However, treatment of heart disease with bone marrow cells and skeletal muscle progenitors has had only marginal positive benefits in clinical trials, perhaps because adult stem cells have limited plasticity. The identification, among human pluripotent stem cells, of early cardiovascular cell progenitors required for the development of the first cardiac lineage would shed light on human cardiogenesis and might pave the way for cell therapy for cardiac degenerative diseases. Here, we report the isolation of an early population of cardiovascular progenitors, characterized by expression of OCT4, stage-specific embryonic antigen 1 (SSEA-1), and mesoderm posterior 1 (MESP1), derived from human pluripotent stem cells treated with the cardiogenic morphogen BMP2. This progenitor population was multipotential and able to generate cardiomyocytes as well as smooth muscle and endothelial cells. When transplanted into the infarcted myocardium of immunosuppressed nonhuman primates, an SSEA-1(+) progenitor population derived from Rhesus embryonic stem cells differentiated into ventricular myocytes and reconstituted 20% of the scar tissue. Notably, primates transplanted with an unpurified population of cardiac-committed cells, which included SSEA-1(-) cells, developed teratomas in the scar tissue, whereas those transplanted with purified SSEA-1(+) cells did not. We therefore believe that the SSEA-1(+) progenitors that we have described here have the potential to be used in cardiac regenerative medicine.