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Wahiba Dhahri1, Tamilla Sadikov Valdman1, Dan Wilkinson2
1McEwen Stem Cell Institute (W.D., T.S.V., E.C., N.A., B.Q., H.M., F.W., E.Q., W.J., S.F., A.M., M.J.G.-G., G.K., M.A.L.), University Health Network, Toronto, ON, Canada.
Circulation
|January 28, 2022
概括
大规模制造成熟的人类多能干细胞衍生的心肌细胞 (hPSC-CMs) 使用聚甲基 (PDMS) 装饰的滚筒瓶改善心脏再生结果. 移植这些成熟的hPSC-CM可促进心肌梗塞后的结构和功能恢复.
科学领域:
- 心血管研究
- 干细胞生物学
- 复原医学
背景情况:
- 人类多能干细胞衍生的心肌细胞 (hPSC-CMs) 对心脏修复有希望,但由于不成熟而受到限制.
- 转化应用需要大规模生产成熟的hPSC-CM.
研究的目的:
- 开发使用聚甲基 (PDMS) 装饰的滚筒瓶的成熟hPSC-CM的可扩展制造.
- 在心肌梗塞模型中评估成熟的hPSC-CM与不成熟的治疗潜力.
主要方法:
- 在PDMS与组织培养塑料上成熟的hPSC-CMs的表型化使用转录学,成像学和电生理学.
- 将hPSC-CM移植到几内亚猪心肌梗塞模型中
- 使用组织学,光学映射,心声学和心电学评估移植结构,功能和整合.
主要成果:
- 每个PDMS装饰的滚筒瓶可产生超过1x10^8个成熟的hPSC-CM.
- 经过PDMS成熟的hPSC-CMs表现出增强的心脏基因表达和体外成熟.
- 移植的PDMS成熟的hPSC-CM显示了移植结构的改善,电机一体化,节律失常的减少,以及功能恢复的改善.
结论:
- 建立了成熟的hPSC-CMs规模生成的实际方法.
- 移植更成熟的hPSC-CM导致了优异的体内结果.
- 这种方法提升了hPSC-CMs对心脏再生的潜力.
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