Large-scale production of human pluripotent stem cell derived cardiomyocytes

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...

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Bibliographic Details
Published in:Advanced drug delivery reviews 2016-01, Vol.96, p.18-30
Main Authors: Kempf, Henning, Andree, Birgit, Zweigerdt, Robert
Format: Article
Language:English
Subjects:
Animals
Bioreactor
Cardiomyocytes
Cell Culture Techniques - instrumentation
Cell Culture Techniques - methods
Cell Differentiation
Differentiation
Human pluripotent stem cells
Humans
Myocytes, Cardiac - cytology
Myocytes, Cardiac - metabolism
Myocytes, Cardiac - transplantation
Pluripotent Stem Cells - cytology
Pluripotent Stem Cells - metabolism
Pluripotent Stem Cells - transplantation
Process development
Scale-up
Stem Cell Research
Tissue Engineering - instrumentation
Tissue Engineering - methods
Wnt Signaling Pathway
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Summary: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. [Display omitted]
ISSN:0169-409X
1872-8294
DOI:10.1016/j.addr.2015.11.016