Journal article
Controlling expansion and cardiomyogenic differentiation of human pluripotent stem cells in scalable suspension culture
H Kempf, R Olmer, C Kropp, M Rückert, M Jara-Avaca, D Robles-Diaz, A Franke, DA Elliott, D Wojciechowski, M Fischer, A Roa Lara, G Kensah, I Gruh, A Haverich, U Martin, R Zweigerdt
Stem Cell Reports | Published : 2014
Abstract
To harness the potential of human pluripotent stem cells (hPSCs), an abundant supply of their progenies is required. Here, hPSC expansion as matrix-independent aggregates in suspension culture was combined with cardiomyogenic differentiation using chemical Wnt pathway modulators. A multiwell screen was scaled up to stirred Erlenmeyer flasks and subsequently to tank bioreactors, applying controlled feeding strategies (batch and cyclic perfusion). Cardiomyogenesis was sensitive to the GSK3 inhibitor CHIR99021 concentration, whereas the aggregate size was no prevailing factor across culture platforms. However, in bioreactors, the pattern of aggregate formation in the expansion phase dominated s..
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Awarded by European Commission
Funding Acknowledgements
We thank T. Scheper for providing basic fibroblast growth factor, A. Kirschning and G. Drager for providing Y-27632 and CHIR99021, A. Haase for providing the iPSC lines, E. Stanley and A. Elefanty for providing the hES-NKX2.5 cell line, and J. Dahlmann for the helpful discussion on microwell-generated aggregates. We thank N. McGuinness for critical reading of the manuscript. We also thank the RCU Transcriptomics of the Hannover Medical School for performing the microarray and their support in analyzing the data. This work was funded by Cluster of Excellence REBIRTH (DFG EXC62/1), German Ministry for Education and Science (BMBF; grant no. 13N12606), and StemBANCC (support from the Innovative Medicines Initiative joint undertaking under grant agreement no 115439-2, resources of which are composed of financial contribution from the European Union [FP7/2007-2013] and EFPIA companies' in kind contribution).