In vitro maturation of cardiomyocytes in 3D is essential for the development of viable cardiac models for therapeutic and developmental studies. The method by which cardiomyocytes undergoes maturation has significant implications for understanding cardiomyocytes biology. The regulation of the extracellular matrix (ECM) by changing the composition and stiffness is quintessential for engineering a suitable environment for cardiomyocytes maturation. In this paper, we demonstrate that collagen type I, a component of the ECM, plays a crucial role in the maturation of cardiomyocytes. To this end, embryonic stem-cell derived cardiomyocytes were incorporated into Matrigel-based hydrogels with varying collagen type I concentrations of 0 mg, 3 mg, and 6 mg. Each hydrogel was analyzed by measuring the degree of stiffness, the expression levels of MLC2v, TBX18, and pre-miR-21, and the size of the hydrogels. It was shown that among the hydrogel variants, the Matrigel-based hydrogel with 3 mg of collagen type I facilitates cardiomyocyte maturation by increasing MLC2v expression. The treatment of transforming growth factor β1 (TGF-β1) or fibroblast growth factor 4 (FGF-4) on the hydrogels further enhanced the MLC2v expression and thereby cardiomyocyte maturation.
Bibliographical noteFunding Information:
We thank Choi at Korea University for sharing the protocol for the maturation of human embryonic stem cell derived cardiomyocytes and Song at Korea University for helping with the revision process. This study was supported by the grant from the National Research Foundation of Korea, Republic of Korea (Grant No. 2016-M3A9B6947892) and a Korea University Grant.
Funding: This study was supported by the grant from the National Research Foundation of Korea, Republic of Korea (Grant No. 2016-M3A9B6947892) and a Korea University Grant.
© 2019 by the authors.
- Cardiomyocyte maturation
- Collagen type I
- Embryonic stem-cell
- Matrigel-based hydrogel
ASJC Scopus subject areas
- Polymers and Plastics