Improving cardiac differentiation of human pluripotent stem cells by targeting ferroptosis

Aalders, Jeffrey; Leger, Laurens; Hassannia, Behrouz; Goossens, Vera; Vanden Berghe, Tom; van Hengel, Jolanda

doi:10.1016/J.RETH.2024.02.007

Title

Improving cardiac differentiation of human pluripotent stem cells by targeting ferroptosis

Author

Aalders, Jeffrey

Leger, Laurens

Hassannia, Behrouz

Goossens, Vera

Vanden Berghe, Tom

van Hengel, Jolanda

Abstract

Generation of cardiomyocytes from human pluripotent stem cells (hPSCs) is of high interest for disease modelling and regenerative medicine. hPSCs can provide an unlimited source of patient-specific cardiomyocytes that are otherwise difficult to obtain from individuals. Moreover, the low proliferation rate of adult cardiomyocytes and low viability ex vivo limits the quantity of study material. Most protocols for the differentiation of cardiomyocytes from hPSCs are based on the temporal modulation of the Wnt pathway. However, during the initial stage of GSK-3 inhibition, a substantial number of cells are lost due to detachment. In this study, we aimed to increase the efficiency of generating cardiomyocytes from hPSCs. We identified cell death as a detrimental factor during this initial stage of in vitro cardiomyocyte differentiation. Through pharmacological targeting of different types of cell death, we discovered that ferroptosis was the main cell death type during the first 48 h of the in vitro differentiation procedure. Inhibiting ferroptosis using ferrostatin-1 during cardiomyocyte differentiation resulted in increased robustness and cell yield. (c) 2024, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).

Language

English

Source (journal)

Regenerative Therapy

Publication

2024

ISSN

23523204

2352-3204

DOI

10.1016/J.RETH.2024.02.007

Volume/pages