Stimulating Calcium Handling in hiPSC-Derived Engineered Cardiac Tissues Enhances Force Production.

ABSTRACT: Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have profound utility in generating functional human engineered cardiac tissues (ECT) for heart repair. However, the field at large is concerned about the relative immaturity of these hiPSC-CMs as we aim to develop clinically relevant models for regenerative therapy and drug testing. Herein, we develop a novel calcium (Ca2+) conditioning protocol that maintains ECTs in a physiological range of Ca2+ and assesses contractility in increasing calcium environments. Lactate-based selection served as a method to purify and shift the metabolic profile of hiPSC-CMs to evaluate the role of metabolism on Ca2+ sensitivity. After 2 weeks, we observe 2-fold greater peak twitch stress in high-Ca2+ conditioned ECTs, despite having lowe

SUBMITTER: Minor AJ 

PROVIDER: S-EPMC8895492 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature