C-stem: Engineering Niche-like Micro-compartments for Optimal and Scale-independent Expansion of Human Pluripotent Stem Cells in Bioreactors
Year: 2021
Type: preprint
Abstract: Human pluripotent stem cells (hPSCs) have emerged as the most promising cellular source for cell therapies. To overcome scale up limitations of classical 2D culture systems, suspension cultures have been developed to meet the need of large-scale culture in regenerative medicine. Despite constant improvements, current protocols relying on the generation of micro-carriers or cell aggregates only achieve moderate amplification performance. Here, guided by reports showing that hPSCs can self-organize in vitro into cysts reminiscent of the epiblast stage in embryo development, we developed a physio-mimetic approach for hPSC culture. We engineered stem cell niche microenvironments inside microfluidics-assisted core-shell microcapsules. We demonstrate that lumenized three-dimensional colonies maximize viability and expansion rates while maintaining pluripotency. By optimizing capsule size and culture conditions, we scale-up this method to industrial scale stirred tank bioreactors and achieve an unprecedented hPSC amplification rate of 282-fold in 6.5 days.
Authors: Philippe J.R. Cohen, Elisa Luquet, Justine Pletenka, Andrea Leonard, Elise Warter, Basile Gurchenkov, Jessica Carrere, Clement Rieu, Jerome Hardouin, Fabien Moncaubeig, Michael Lanero, Eddy Quelennec, Helene Wurtz, Emilie Jamet, Maelle Demarco, Celine banal, Paul Van Liedekerke, Pierre Nassoy, Maxime Feyeux, Nathalie Lefort, kevin Alessandri
Institutions: Inserm, Université Paris Cité, Institut des Maladies Génétiques Imagine, Institut du Cerveau, Institut national de recherche en sciences et technologies du numérique, Sorbonne Université, Laboratoire Jacques-Louis Lions, Centre National de la Recherche Scientifique, Université de Bordeaux, Institut d’Optique Graduate School, Laboratoire Photonique, Numérique et Nanosciences
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3182986992