Creating frog heart as an organ: in vitro-induced heart functions as a circulatory organ in vivo
Creating frog heart as an organ: in vitro-induced heart functions as a circulatory organ in vivo
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DOI：
10.1387/ijdb.093036mk
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发表时间：
2010-01-01
影响因子：
0.7
通讯作者：
Asashima, Makoto
中科院分区：
文献类型：
--
作者：
Kinoshita, Masayoshi;Ariizumi, Takashi;Asashima, Makoto
心肌细胞是由多种多能细胞，如胚胎干细胞和骨髓干细胞诱导的；然而，二维细胞片以外的心脏组织的生成尚未见报道。在实现心脏再生医学方面，人们期待已久的下一步是创造出心脏独有的高阶三维结构。我们之前已经证明，从非洲爪蟾胚胎中切除的未分化细胞（动物帽）可以在体外诱导心肌细胞。心肌细胞是通过先分离动物帽，然后在激活素处理下重新聚集来诱导的。在这里，我们描述了一种在体内创造完整异位心脏的有趣方法，包括在早期胚胎发生期间引入体外创造的组织。因此，将动物帽聚集体移植到神经后期胚胎的腹部，形成两室心脏。双心幼虫在移植心脏完好的情况下成熟为成年动物。移植心脏累及体循环得到证实。此外，异位心脏具有心房和心室等高阶结构，在形态学、组织学和电生理上与原心脏相同。该系统将促进心脏器官发生的研究，并可能促进临床应用从组织工程向器官工程的转变。
Cardiomyocytes have been induced from various pluripotent cells, such as embryonic stem cells and myeloid stem cells; however, the generation of cardiac tissues beyond two-dimensional cell-sheets has not been reported. Creating higher order, three-dimensional structures that are unique to heart is the long-awaited next step in realizing cardiac regenerative medicine. We have previously shown that cardiomyocytes can be induced in vitro from undifferentiated cells (animal caps) excised from Xenopus embryos. Cardiomyocytes were induced by first dissociating the animal caps and then reaggregating them following treatment with activin. Here, we describe an interesting method for creating a complete ectopic heart in vivo, involving the introduction of in vitro-created tissue during early embryogenesis. Thus, animal cap reaggregates were transplanted into the abdomen of late-neurula-stage embryos, resulting in two-chambered hearts being formed. The dual-heart larvae matured into adult animals with transplanted hearts intact. Involvement of transplanted hearts in systemic circulation was demonstrated. Moreover, the ectopic hearts possessed higher order structures such as atrium and ventricle, and were morphologically, histologically, and electrophysiologically identical to original hearts. This system should facilitate the study of heart organogenesis and may promote a shift from tissue to organ engineering for clinical applications.