DataVXAdvanced SciencePaper
journal article·2025-03Open access

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

Pedro Vicente, Lara R. Inocêncio, Asier Ullate‐Agote, Ana F. Louro, João Jacinto, Beatriz Gamelas, Olalla Iglesias‐García, Patxi San Martin‐Uriz, Paula Aguirre‐Ruiz, Gonzalo R. Ríos‐Muñoz, María Eugenia Fernández‐Santos, Alain van Mil, Joost P. G. Sluijter, Felipe Prósper, Manuel M Mazo Vega, Paula M. Alves, Margarida Serra

Advanced Science· Volume 12· Issue 11
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Source abstract

Abstract

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% O 2 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) maintaining constant power input per volume as a scale‐up criteria is demonstrated. After expansion, hiPSC‐CM further mature in culture, revealing more mature transcriptional signatures, higher sarcomere alignment and improved calcium handling. This new bioprocess opens the door to time‐ and cost‐effective generation of hiPSC‐CM.
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Research context

OpenAlex topics: Pluripotent Stem Cells Research · Tissue Engineering and Regenerative Medicine · 3D Printing in Biomedical Research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

iBET Instituto de Biologia Experimental e Tecnológica Apartado 12 Oeiras 2780901 Portugal

Instituto de Tecnologia Química e Biológica António Xavier Universidade de Nova de Lisboa Av. da República Oeiras 2780157 Portugal

Program of Biomedical Engineering Technological Innovation Division CIMA Universidad de Navarra, and Instituto de Investigación Sanitaria de Navarra (IdiSNA) Pamplona 31008 Spain

Hemato‐oncology Program Cancer Division CIMA Universidad de Navarra, and Instituto de Investigación Sanitaria de Navarra (IdiSNA) Pamplona 31008 Spain

Bioengineering Department Universidad Carlos III de Madrid Madrid 28911 Spain

Department of Cardiology Gregorio Marañón Health Research Institute (IiSGM) Hospital General Universitario Gregorio Marañón Madrid 28007 Spain

Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV) Instituto Carlos III Madrid 28029 Spain

Regenerative Medicine Center Utrecht Laboratory of Experimental Cardiology, Circulatory Health Research Center, University Utrecht University Medical Center Utrecht University Utrecht Utrecht 3508 GA The Netherlands

Hematology and Cell Therapy Clínica Universidad de Navarra Pamplona 31008 Spain

Centro de Investigación Biomédica en Red Cáncer (CIBERONC) Madrid 28029 Spain

Funding

Horizon 2020 · Fundação para a Ciência e a Tecnologia · Instituto de Salud Carlos III · Ministerio de Ciencia, Innovación y Universidades

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