z-logo
open-access-imgOpen Access
Universal Cardiac Induction of Human Pluripotent Stem Cells in Two and Three‐Dimensional Formats: Implications for In Vitro Maturation
Author(s) -
Zhang Miao,
Schulte Jan Sebastian,
Heinick Alexander,
Piccini Ilaria,
Rao Jyoti,
Quaranta Roberto,
Zeuschner Dagmar,
Malan Daniela,
Kim KeePyo,
Röpke Albrecht,
Sasse Philipp,
AraúzoBravo Marcos,
Seebohm Guiscard,
Schöler Hans,
Fabritz Larissa,
Kirchhof Paulus,
Müller Frank Ulrich,
Greber Boris
Publication year - 2015
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1964
Subject(s) - induced pluripotent stem cell , biology , transcriptome , microbiology and biotechnology , computational biology , cellular differentiation , stem cell , gene expression , human induced pluripotent stem cells , cell culture , embryonic stem cell , gene , genetics
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. S tem C ells 2015;33:1456–1469

The content you want is available to Zendy users.

Already have an account? Click here to sign in.
Having issues? You can contact us here