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Enhanced structural maturation of human induced pluripotent stem cell-derived cardiomyocytes under a controlled microenvironment in a microfluidic system

: Kolanowski, Tomasz Jan; Busek, Mathias; Schubert, Mario; Dmitrieva, Anna; Binnewerg, Björn; Pöche, Jessie; Fisher, Konstanze; Schmieder, Florian; Grünzner, Stefan; Hansen, Sinah; Richter, Andreas; El-Armouche, Ali; Sonntag, Frank; Guan, Kaomei


Acta biomaterialia 102 (2020), pp.273-286
ISSN: 1742-7061
ISSN: 1878-7568
Journal Article
Fraunhofer IWS ()
microfluidic system; oxygen control; hemodynamic force; maturation; human induced pluripotent stem cell-derived cardiomyocytes

The lack of a fully developed human cardiac model in vitro hampers the progress of many biomedical research fields including pharmacology, developmental biology, and disease modeling. Currently, available methods may only differentiate human induced pluripotent stem cells (iPSCs) into immature cardiomyocytes. To achieve cardiomyocyte maturation, appropriate modulation of cellular microenvironment is needed. This study aims to optimize a microfluidic system that enhances maturation of human iPSC-derived cardiomyocytes (iPSC-CMs) through cyclic pulsatile hemodynamic forces. Human iPSC-CMs cultured in the microfluidic system show increased alignment and contractility and appear more rod-like shaped with increased cell size and increased sarcomere length when compared to static cultures. Increased complexity and density of the mitochondrial network in iPSC-CMs cultured in the microfluidic system are in line with expression of mitochondrial marker genes MT-CO1 and OPA1. Moreover, the optimized microfluidic system is capable of stably maintaining controlled oxygen levels and inducing hypoxia, revealed by increased expression of HIF1α and EGLN2 as well as changes in contraction parameters in iPSC-CMs. In summary, this microfluidic system boosts the structural maturation of iPSC-CM culture and could serve as an advanced in vitro cardiac model for biomedical research in the future.