title: Large-scale production of human pluripotent stem cell derived cardiomyocytes.
abstract: Regenerative medicine, including preclinical studies in large animal models and tissue engineering approaches as well as innovative assays for drug discovery, will require the constant supply of hPSC-derived cardiomyocytes and other functional progenies. Respective cell production processes must be robust, economically viable and ultimately GMP-compliant. Recent research has enabled transition of lab scale protocols for hPSC expansion and cardiomyogenic differentiation towards more controlled processing in industry-compatible culture platforms. Here, advanced strategies for the cultivation and differentiation of hPSCs will be reviewed by focusing on stirred bioreactor-based techniques for process upscaling. We will discuss how cardiomyocyte mass production might benefit from recent findings such as cell expansion at the cardiovascular progenitor state. Finally, remaining challenges will be highlighted, specifically regarding three dimensional (3D) hPSC suspension culture and critical safety issues ahead of clinical translation.
authors.affiliation: Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiac, Thoracic-, Transplantation and Vascular Surgery, Hannover Medical School, Germany; REBIRTH-Cluster of Excellence, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Electronic address: Kempf.Henning@mh-hannover.de.
authors.forename: Henning
authors.initials: H
authors.lastname: Kempf
authors.affiliation: Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiac, Thoracic-, Transplantation and Vascular Surgery, Hannover Medical School, Germany; REBIRTH-Cluster of Excellence, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Electronic address: Andree.Birgit@mh-hannover.de.
authors.forename: Birgit
authors.initials: B
authors.lastname: Andree
authors.affiliation: Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiac, Thoracic-, Transplantation and Vascular Surgery, Hannover Medical School, Germany; REBIRTH-Cluster of Excellence, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Electronic address: Zweigerdt.Robert@mh-hannover.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Zweigerdt
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods*; D002454:Cell Differentiation; D006801:Humans; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D057905:Stem Cell Research; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods*; D060449:Wnt Signaling Pathway
keywords: Bioreactor; Cardiomyocytes; Differentiation; Human pluripotent stem cells; Process development; Scale-up