Scaffold-free human cardiac tissue patch created from embryonic stem cells.
Scaffold-free human cardiac tissue patch created from embryonic stem cells.
复制标题
由胚胎干细胞产生的无脚手架的人类心脏组织斑块。
DOI：
10.1089/ten.tea.2008.0151
复制
发表时间：
2009-06
影响因子：
--
通讯作者：
Murry CE
中科院分区：
文献类型：
--
作者：
Stevens KR;Pabon L;Muskheli V;Murry CE
心脏组织工程的进展受到以下因素的限制：（1）细胞和宿主对生物材料支架的不良反应，（2）缺乏合适的人心肌细胞来源，以及（3）缺乏可规模生产工程化组织构建体的制造技术。在这里，我们报告了一种新的和可扩展的方法来产生无支架的人类心脏组织补丁。使用激活素A和BMP 4将人胚胎干细胞分化为心肌细胞，并置于旋转定轨振荡器上的悬浮液中。2天后，细胞聚集形成跳动组织的肉眼可见的盘状斑块。贴片直径与输入细胞数量成正比（大约11 mm，1200万个细胞），贴片厚度为300-600 µm。心肌细胞集中在贴片边缘周围，并随着时间的推移表现出纯度和成熟度的增加，11天后约占总细胞的80%。非心脏细胞成分，主要是上皮细胞，在第2天出现，但在以后的时间点显着减少。心肌细胞增殖发生在整个补丁在第2天，但下降到第8天。补丁表现出自律性和同步钙瞬变，表明机电耦合。这些新的无支架人类心肌补片解决了与人类细胞来源和组织制造相关的关键挑战，这些挑战以前抑制了心脏组织工程的进展。
Progress in cardiac tissue engineering has been limited by (1) unfavorable cell and host responses to biomaterial scaffolds, (2) lack of suitable human cardiomyocyte sources, and (3) lack of fabrication techniques for scalable production of engineered tissue constructs. Here we report a novel and scalable method to generate scaffold-free human cardiac tissue patches. Human embryonic stem cells were differentiated to cardiomyocytes using activin A and BMP4 and placed into suspension on a rotating orbital shaker. Cells aggregated to form macroscopic disc-shaped patches of beating tissue after 2 days. Patch diameter was directly proportional to input cell number (approximately 11 mm with 12 million cells), and patches were 300–600 µm thick. Cardiomyocytes were concentrated around the patch edges and exhibited increased purity and maturation with time, comprising approximately 80% of total cells after 11 days. Noncardiac cell elements, primarily epithelium, were present at day 2 but were diminished markedly at later time points. Cardiomyocyte proliferation occurred throughout the patches at day 2 but declined by day 8. Patches exhibited automaticity and synchronous calcium transients, indicating electromechanical coupling. These novel scaffold-free human myocardial patches address critical challenges related to human cell sourcing and tissue fabrication that previously inhibited progress in cardiac tissue engineering.
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影响因子：
5
作者：
McDevitt, TC;Laflamme, MA;Murry, CE
通讯作者：
Murry, CE
影响因子：
6
作者：
Laflamme, MA;Gold, J;Murry, CE
通讯作者：
Murry, CE
影响因子：
4.8
作者：
Eschenhagen, T;Fink, C;Elson, EL
通讯作者：
Elson, EL
影响因子：
24
作者：
Caspi, Oren;Huber, Irit;Gepstein, Lior
通讯作者：
Gepstein, Lior
影响因子：
3.8
作者：
Carrier, RL;Rupnick, M;Vunjak-Novakovic, G
通讯作者：
Vunjak-Novakovic, G