Extracellular matrix formation after transplantation of human embryonic stem cell-derived cardiomyocytes.
Extracellular matrix formation after transplantation of human embryonic stem cell-derived cardiomyocytes.
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DOI：
10.1007/s00018-009-0179-z
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发表时间：
2010-01
影响因子：
8
通讯作者：
Mummery, Christine L.
中科院分区：
文献类型：
--
作者：
van Laake, L. W.;van Donselaar, E. G.;Monshouwer-Kloots, J.;Schreurs, C.;Passier, R.;Humbel, B. M.;Doevendans, P. A.;Sonnenberg, A.;Verkleij, A. J.;Mummery, Christine L.
移植人胚胎干细胞衍生的心肌细胞（hESC-CM）用于心脏再生会因移植物周围纤维化组织的形成而受到阻碍，从而阻碍电生理耦合。通过研究这个过程，我们发现：（1）在体外敲打的 hESC-CM 嵌入胶原蛋白、层粘连蛋白和纤连蛋白中，它们通过适当的整合素结合； (2)移植入小鼠心脏后，hESC-CM继续分泌胶原IV、XVIII和纤连蛋白； (3) hESC-CM上的整合素表达与它们在体内遇到或分泌的基质类型很大程度上匹配； (4) hESC衍生的内皮细胞和/或心脏祖细胞与hESC-CM共移植导致功能性毛细血管的形成； (5) 移植的 hESC-CM 在体内存活并成熟至少 24 周。这些结果构成了未来发展的基础，旨在减少目前使基于细胞的心脏病治疗复杂化的不良纤维化反应，并为通过共移植内皮细胞成功植入心肌细胞提供额外的线索。本文的在线版本 (doi:10.1007/s00018-009-0179-z) 包含补充材料，可供授权用户使用。
Transplantation of human embryonic stem cell-derived cardiomyocytes (hESC-CM) for cardiac regeneration is hampered by the formation of fibrotic tissue around the grafts, preventing electrophysiological coupling. Investigating this process, we found that: (1) beating hESC-CM in vitro are embedded in collagens, laminin and fibronectin, which they bind via appropriate integrins; (2) after transplantation into the mouse heart, hESC-CM continue to secrete collagen IV, XVIII and fibronectin; (3) integrin expression on hESC-CM largely matches the matrix type they encounter or secrete in vivo; (4) co-transplantation of hESC-derived endothelial cells and/or cardiac progenitors with hESC-CM results in the formation of functional capillaries; and (5) transplanted hESC-CM survive and mature in vivo for at least 24 weeks. These results form the basis of future developments aiming to reduce the adverse fibrotic reaction that currently complicates cell-based therapies for cardiac disease, and to provide an additional clue towards successful engraftment of cardiomyocytes by co-transplanting endothelial cells. The online version of this article (doi:10.1007/s00018-009-0179-z) contains supplementary material, which is available to authorized users.
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