Universität zu Köln

Correia, Claudia, Serra, Margarida ORCID: 0000-0001-5013-6625, Espinha, Nuno, Sousa, Marcos, Brito, Catarina ORCID: 0000-0002-8926-279X, Burkert, Karsten, Zheng, Yunjie, Hescheler, Juergen, Carrondo, Manuel J. T., Saric, Tomo ORCID: 0000-0001-8344-1095 and Alves, Paula M. (2014). Combining Hypoxia and Bioreactor Hydrodynamics Boosts Induced Pluripotent Stem Cell Differentiation Towards Cardiomyocytes. Stem Cell Rev. Rep., 10 (6). S. 786 - 802. TOTOWA: HUMANA PRESS INC. ISSN 1558-6804

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Abstract

Cardiomyocytes (CMs) derived from induced pluripotent stem cells (iPSCs) hold great promise for patient-specific disease modeling, drug screening and cell therapy. However, existing protocols for CM differentiation of iPSCs besides being highly dependent on the application of expensive growth factors show low reproducibility and scalability. The aim of this work was to develop a robust and scalable strategy for mass production of iPSC-derived CMs by designing a bioreactor protocol that ensures a hypoxic and mechanical environment. Murine iPSCs were cultivated as aggregates in either stirred tank or WAVE bioreactors. The effect of dissolved oxygen and mechanical forces, promoted by different hydrodynamic environments, on CM differentiation was evaluated. Combining a hypoxia culture (4 % O-2 tension) with an intermittent agitation profile in stirred tank bioreactors resulted in an improvement of about 1000-fold in CM yields when compared to normoxic (20% O-2 tension) and continuously agitated cultures. Additionally, we showed for the first time that wave-induced agitation enables the differentiation of iPSCs towards CMs at faster kinetics and with higher yields (60 CMs/input iPSC). In an 11-day differentiation protocol, clinically relevant numbers of CMs (2.3x10(9) CMs/1 L) were produced, and CMs exhibited typical cardiac sarcomeric structures, calcium transients, electrophysiological profiles and drug responsiveness. This work describes significant advances towards scalable cardiomyocyte differentiation of murine iPSC, paving the way for the implementation of this strategy for mass production of their human counterparts and their use for cardiac repair and cardiovascular research.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Correia, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Serra, Margarida UNSPECIFIED orcid.org/0000-0001-5013-6625 UNSPECIFIED Espinha, Nuno UNSPECIFIED UNSPECIFIED UNSPECIFIED Sousa, Marcos UNSPECIFIED UNSPECIFIED UNSPECIFIED Brito, Catarina UNSPECIFIED orcid.org/0000-0002-8926-279X UNSPECIFIED Burkert, Karsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Zheng, Yunjie UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Carrondo, Manuel J. T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Saric, Tomo UNSPECIFIED orcid.org/0000-0001-8344-1095 UNSPECIFIED Alves, Paula M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-422888
DOI:	10.1007/s12015-014-9533-0
Journal or Publication Title:	Stem Cell Rev. Rep.
Volume:	10
Number:	6
Page Range:	S. 786 - 802
Date:	2014
Publisher:	HUMANA PRESS INC
Place of Publication:	TOTOWA
ISSN:	1558-6804
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CARDIAC DIFFERENTIATION; OXYGEN-TENSION; CULTURE; MOUSE; GENERATION; EXPANSION Multiple languages Cell & Tissue Engineering; Cell Biology; Medicine, Research & Experimental Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42288