Simulated microgravity improves maturation of cardiomyocytes derived from human induced pluripotent stem cells.

Autor: Forghani P; Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, 2015 Uppergate Drive, Atlanta, GA, 30322, USA., Rashid A; Biomolecular Chemistry, Department of Chemistry, Emory University, Atlanta, GA, 30322, USA., Armand LC; Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, 2015 Uppergate Drive, Atlanta, GA, 30322, USA., Wolfson D; Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, 2015 Uppergate Drive, Atlanta, GA, 30322, USA., Liu R; Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, 2015 Uppergate Drive, Atlanta, GA, 30322, USA., Cho HC; Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, 2015 Uppergate Drive, Atlanta, GA, 30322, USA.; Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, 30322, USA., Maxwell JT; Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, 2015 Uppergate Drive, Atlanta, GA, 30322, USA., Jo H; Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, 2015 Uppergate Drive, Atlanta, GA, 30322, USA.; Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, 30322, USA., Salaita K; Biomolecular Chemistry, Department of Chemistry, Emory University, Atlanta, GA, 30322, USA.; Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, 30322, USA., Xu C; Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, 2015 Uppergate Drive, Atlanta, GA, 30322, USA. chunhui.xu@emory.edu.; Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, 30322, USA. chunhui.xu@emory.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Jan 26; Vol. 14 (1), pp. 2243. Date of Electronic Publication: 2024 Jan 26.
DOI: 10.1038/s41598-024-52453-1
Abstrakt: Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) possess tremendous potential for basic research and translational application. However, these cells structurally and functionally resemble fetal cardiomyocytes, which is a major limitation of these cells. Microgravity can significantly alter cell behavior and function. Here we investigated the effect of simulated microgravity on hiPSC-CM maturation. Following culture under simulated microgravity in a random positioning machine for 7 days, 3D hiPSC-CMs had increased mitochondrial content as detected by a mitochondrial protein and mitochondrial DNA to nuclear DNA ratio. The cells also had increased mitochondrial membrane potential. Consistently, simulated microgravity increased mitochondrial respiration in 3D hiPSC-CMs, as indicated by higher levels of maximal respiration and ATP content, suggesting improved metabolic maturation in simulated microgravity cultures compared with cultures under normal gravity. Cells from simulated microgravity cultures also had improved Ca 2+ transient parameters, a functional characteristic of more mature cardiomyocytes. In addition, these cells had improved structural properties associated with more mature cardiomyocytes, including increased sarcomere length, z-disc length, nuclear diameter, and nuclear eccentricity. These findings indicate that microgravity enhances the maturation of hiPSC-CMs at the structural, metabolic, and functional levels.
(© 2024. The Author(s).)
Databáze: MEDLINE
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