从人胎盘中发现一种多能细胞。

Sangeetha Vadakke-Madathil, Esmaa Bouhamida, Bingyan Wang, Prabhu Mathiyalagan, Micayla Oniskey, Carlos Santos-Gallego, Michael Hadley, Lori Croft, Fumiko Dekio, Rachel Brody, Shari Gelber, Rhoda Sperling, Hina W Chaudhry
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摘要

我们首次报道了从人类胎盘中分离出的一组独特的多能细胞,它们可以分化为具有克隆增殖能力、迁移能力和免疫特权转录组学证据的心肌细胞和血管细胞。尾型同源盒-2(CDX2)是一种保守因子,在胚胎早期发育过程中调节滋养细胞外胚层的形成和胎盘形成,但以前从未涉及发育保守的再生机制。我们早些时候报道,在患有实验性心脏损伤(心肌梗死)的雄性小鼠中,小鼠胎盘中的Cdx2谱系细胞能够在静脉注射后恢复心脏功能。在这里,我们证明了CDX2表达细胞在人绒毛膜中普遍存在,并准备进行心血管分化。我们检测了106名健康患者的胎盘,发现分离的CDX2细胞可以自发分化为心肌细胞、功能性血管细胞,并在体外保持归巢能力。转录组学分析的功能注释支持CDX2细胞中增强的心脏生成、血管生成、免疫调节和趋化性基因特征。CDX2细胞可以在保持心血管分化的培养基中克隆繁殖。我们的数据支持在心血管疾病治疗策略的设计中进一步使用这种可获得且符合伦理的细胞源。
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Discovery of a multipotent cell type from the term human placenta.

We report a population of multipotent cells isolated from term human placentas, for the first time, that differentiates into cardiomyocytes and vascular cells with clonal ability, migratory ability, and trancriptomic evidence of immune privilege. Caudal-type homeobox-2 (CDX2) is a conserved factor that regulates trophectoderm formation and placentation during early embryonic development but has not previously been implicated in developmentally conserved regenerative mechanisms. We earlier reported that murine Cdx2 cells restored cardiac function after intravenous delivery in male mice with experimental myocardial infarction (MI). Here we demonstrate that CDX2 cells found in human chorion are poised for cardiovascular differentiation. We isolated CDX2 cells from term placentas of 150 healthy patients and showed that they spontaneously differentiate into cardiomyocytes, functional vascular cells, and retain homing ability in vitro with a transcriptome that supports enhanced cardiogenesis, vasculogenesis, immune modulation, and chemotaxis gene signatures. They restore cardiac function when administered to NOD/SCID mice subjected to MI. CDX2 cells can be clonally propagated in culture with retention of cardiovascular differentiation. Our data compels further use of this ethically feasible cell source in the design of therapeutic strategies for cardiovascular disease.

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