Billion-Scale Expansion of Functional hiPSC-Derived Cardiomyocytes in Bioreactors Through Oxygen Control and Continuous Wnt Activation.

ABSTRACT: Generation of upscaled quantities of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), for therapeutic or testing applications, is both expensive and time-consuming. Herein, a scalable bioprocess for hiPSC-CM expansion in stirred-tank bioreactors (STB) is developed. By combining the continuous activation of the Wnt pathway, through perfusion of CHIR99021, within a mild hypoxia environment, the expansion of hiPSC-CM as aggregates is maximized, reaching 4 billion of pure hiPSC-CM in 2L STB. In particular, the importance of i) controlling the dissolved oxygen at 10% O₂ to reduce reactive oxygen species production and upregulate genes involved in cell proliferation, resulting in higher expansion rates (tenfold) compared to normoxic conditions, and ii) maintainin

SUBMITTER: Vicente P 

PROVIDER: S-EPMC11923921 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature