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          Institute: MPI für molekulare Biomedizin     Collection: Jahrbuch 2016 (publ. 2015, arch)     Display Documents



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ID: 717246.0, MPI für molekulare Biomedizin / Jahrbuch 2016 (publ. 2015, arch)
Universal cardiac induction of human pluripotent stem cells in two and three-dimensional formats: implications for in vitro maturation
Authors:Zhang, M.; Schulte, J. S.; Heinick, A.; Piccini, I.; Rao, J.; Quaranta, R.; Zeuschner, D.; Malan, D.; Kim, K. P.; Ropke, A.; Sasse, P.; Arauzo-Bravo, M.; Seebohm, G.; Scholer, H.; Fabritz, L.; Kirchhof, P.; Muller, F. U.; Greber, B.
Date of Publication (YYYY-MM-DD):2015-05
Title of Journal:Stem Cells
Volume:33
Issue / Number:5
Start Page:1456
End Page:1469
Review Status:Internal review
Audience:Not Specified
Abstract / Description:Directed cardiac differentiation of human pluripotent stem cells (hPSCs) enables disease modeling, investigation of human cardiogenesis, as well as large-scale production of cardiomyocytes (CMs) for translational purposes. Multiple CM differentiation protocols have been developed to individually address specific requirements of these diverse applications, such as enhanced purity at a small scale or mass production at a larger scale. However, there is no universal high-efficiency procedure for generating CMs both in two-dimensional (2D) and three-dimensional (3D) culture formats, and undefined or complex media additives compromise functional analysis or cost-efficient upscaling. Using systematic combinatorial optimization, we have narrowed down the key requirements for efficient cardiac induction of hPSCs. This implied differentiation in simple serum and serum albumin-free basal media, mediated by a minimal set of signaling pathway manipulations at moderate factor concentrations. The method was applicable both to 2D and 3D culture formats as well as to independent hPSC lines. Global time-course gene expression analyses over extended time periods and in comparison with human heart tissue were used to monitor culture-induced maturation of the resulting CMs. This suggested that hPSC-CMs obtained with our procedure reach a rather stable transcriptomic state after approximately 4 weeks of culture. The underlying gene expression changes correlated well with a decline of immature characteristics as well as with a gain of structural and physiological maturation features within this time frame. These data link gene expression patterns of hPSC-CMs to functional readouts and thus define the cornerstones of culture-induced maturation.
Free Keywords:cardiac differentiation; human pluripotent stem cells; in-vitro maturation
External Publication Status:published
Document Type:Article
Communicated by:Keuker
Affiliations:MPI für molekulare Biomedizin
Identifiers:ISSN:1549-4918 (Electronic) 1066-5099 (Linking) %R 10.1... [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/25639979 [ID No:2]
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