Physiological calcium combined with electrical pacing accelerates maturation of human engineered heart tissue

被引：22
|
作者：
Shen, Shi [1 ]
Sewanan, Lorenzo R. [2 ]
Shao, Stephanie [1 ]
Halder, Saiti S. [1 ]
Stankey, Paul [3 ,4 ]
Li, Xia [1 ]
Campbell, Stuart G. [1 ,5 ]
机构：
[1] Yale Univ, Dept Biomed Engn, 55 Prospect St MEC 211, New Haven, CT 06511 USA
[2] Columbia Univ Irving Med Ctr, Dept Med, New York, NY USA
[3] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA USA
[4] Harvard Univ, John A Paulson Sch Engn & Appl Sci, Cambridge, MA USA
[5] Yale Univ, Dept Cellular & Mol Physiol, New Haven, CT 06520 USA
来源：
STEM CELL REPORTS | 2022年 / 17卷 / 09期
基金：
美国国家科学基金会;
关键词：
FORCE-FREQUENCY-RELATIONSHIP; CELL-DERIVED CARDIOMYOCYTES; TROPONIN-I; PHOSPHOLAMBAN; EXPRESSION;
D O I：
10.1016/j.stemcr.2022.07.006
中图分类号：
Q813 [细胞工程];
学科分类号：
摘要：
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have wide potential application in basic research, drug discovery, and regenerative medicine, but functional maturation remains challenging. Here, we present a method whereby maturation of hiPSC-CMs can be accelerated by simultaneous application of physiological Ca2+ and frequency-ramped electrical pacing in culture. This combination produces positive force-frequency behavior, physiological twitch kinetics, robust b-adrenergic response, improved Ca2+ handling, and cardiac troponin I expression within 25 days. This study provides insights into the role of Ca2+ in hiPSC-CM maturation and offers a scalable platform for translational and clinical research.
引用
收藏
页码：2037 / 2049
页数：13
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