Engineering Scalable Manufacturing of High-Quality Stem Cell-Derived Cardiomyocytes for Cardiac Tissue Repair.

Engineering Scalable Manufacturing of High-Quality Stem Cell-Derived Cardiomyocytes for Cardiac Tissue Repair.
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DOI:
10.3389/fmed.2018.00110
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发表时间:
2018
影响因子:
3.9
通讯作者:
Palecek SP
Palecek SP
中科院分区:
医学3区
文献类型:
--
作者:
Dunn KK;Palecek SP

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人类多能干细胞 (hPSC) 衍生的心肌细胞 (CM) 分化和生产的最新进展刺激了在人类心脏再生治疗中使用这些细胞的策略的发展。 hPSC 衍生的 CM 进行临床试验和转化实施的先决条件是能够以替代心脏病期间损失的细胞所需的规模生产安全、有效的细胞。目前的分化方案产生具有致心律失常潜力的胎儿样 CM。这些 hPSC 衍生的 CM 尚未充分成熟,无法将这些细胞用作再生医学疗法。对心脏发育过程中天然心脏环境的深入了解可能有助于设计指导 hPSC 衍生的 CM 成熟的策略。具体来说,必须考虑开发方法,将天然细胞间相互作用和生物力学线索纳入 hPSC 衍生的 CM 生产中,从而有利于扩大规模。
Recent advances in the differentiation and production of human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) have stimulated development of strategies to use these cells in human cardiac regenerative therapies. A prerequisite for clinical trials and translational implementation of hPSC-derived CMs is the ability to manufacture safe and potent cells on the scale needed to replace cells lost during heart disease. Current differentiation protocols generate fetal-like CMs that exhibit proarrhythmogenic potential. Sufficient maturation of these hPSC-derived CMs has yet to be achieved to allow these cells to be used as a regenerative medicine therapy. Insights into the native cardiac environment during heart development may enable engineering of strategies that guide hPSC-derived CMs to mature. Specifically, considerations must be made in regard to developing methods to incorporate the native intercellular interactions and biomechanical cues into hPSC-derived CM production that are conducive to scale-up.