Parthenogenetic stem cells for tissue-engineered heart repair
Parthenogenetic stem cells for tissue-engineered heart repair
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DOI：
10.1172/jci66854
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发表时间：
2013-03-01
影响因子：
15.9
通讯作者：
Zimmermann, Wolfram-Hubertus
中科院分区：
文献类型：
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作者：
Didie, Michael;Christalla, Peter;Zimmermann, Wolfram-Hubertus
单亲单性生殖被认为是体外受精的一种不需要的副产品。在子宫内单性生殖体的发育受到器官发生缺陷，特别是心脏发生缺陷的严重损害。虽然发育受损，但显然多能干细胞可以来自孤雌胚泡。在这里，我们假设，非胚胎孤雌生殖干细胞（PSC）可以直接向心脏谱系和应用于组织工程心脏修复。我们首先证实了小鼠PSC和胚胎干细胞（ESC）的基本特性相似，尽管在遗传（等位基因变异性）和表观遗传（差异印迹）特征方面存在显着差异。PSC中主要组织相容性复合物（MHC）的单倍性对于基于同种异体细胞的疗法特别有吸引力。因此，我们证实了PSC在MHC匹配的同种异体移植中的可接受性。从PSC和ESC衍生的心肌细胞同样有效。心肌细胞限制性GFP的使用使得能够在体外和体内进行细胞分选和记录高级结构和功能成熟。这包括PSC衍生的心肌细胞与受体心肌的无缝电整合。最后，我们富集心肌细胞以促进力产生心肌的工程，并证明了这种技术在心肌梗死后增强局部心肌功能的实用性。总的来说，我们的数据证明了多能性，在PSC中具有不受限制的心脏发生性，并将这种独特的细胞类型作为组织工程心脏修复的有吸引力的来源。
Uniparental parthenotes are considered an unwanted byproduct of in vitro fertilization. In utero parthenote development is severely compromised by defective organogenesis and in particular by defective cardiogenesis. Although developmentally compromised, apparently pluripotent stem cells can be derived from parthenogenetic blastocysts. Here we hypothesized that nonembryonic parthenogenetic stem cells (PSCs) can be directed toward the cardiac lineage and applied to tissue-engineered heart repair. We first confirmed similar fundamental properties in murine PSCs and embryonic stem cells (ESCs), despite notable differences in genetic (allelic variability) and epigenetic (differential imprinting) characteristics. Haploidentity of major histocompatibility complexes (MHCs) in PSCs is particularly attractive for allogeneic cell-based therapies. Accordingly, we confirmed acceptance of PSCs in MHC-matched allotransplantation. Cardiomyocyte derivation from PSCs and ESCs was equally effective. The use of cardiomyocyte-restricted GFP enabled cell sorting and documentation of advanced structural and functional maturation in vitro and in vivo. This included seamless electrical integration of PSC-derived cardiomyocytes into recipient myocardium. Finally, we enriched cardiomyocytes to facilitate engineering of force-generating myocardium and demonstrated the utility of this technique in enhancing regional myocardial function after myocardial infarction. Collectively, our data demonstrate pluripotency, with unrestricted cardiogenicity in PSCs, and introduce this unique cell type as an attractive source for tissue-engineered heart repair.