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

Shi Shen; Lorenzo R Sewanan; Stephanie Shao; Saiti S Halder; Paul Stankey; Xia Li; Stuart G Campbell

doi:10.1016/j.stemcr.2022.07.006

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

Stem Cell Reports. 2022 Sep 13;17(9):2037-2049. doi: 10.1016/j.stemcr.2022.07.006. Epub 2022 Aug 4.

Authors

Shi Shen¹, Lorenzo R Sewanan², Stephanie Shao¹, Saiti S Halder¹, Paul Stankey³, Xia Li¹, Stuart G Campbell⁴

Affiliations

¹ Department of Biomedical Engineering, Yale University, 55 Prospect St. MEC 211, New Haven, CT 06511, USA.
² Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
³ Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.
⁴ Department of Biomedical Engineering, Yale University, 55 Prospect St. MEC 211, New Haven, CT 06511, USA; Department of Cellular and Molecular Physiology, Yale University, New Haven, CT, USA. Electronic address: stuart.campbell@yale.edu.

Abstract

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 β-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.

Keywords: calcium; engineered heart tissue; force-frequency relationship; maturation; pacing.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Calcium* / metabolism
Cell Differentiation / physiology
Humans
Induced Pluripotent Stem Cells*
Myocytes, Cardiac
Tissue Engineering / methods

Substances

Calcium

Abstract

Publication types

MeSH terms

Substances

Grants and funding