Surface geometry of poly(ether imide) boosts mouse pluripotent stem cell spontaneous cardiomyogenesis via modulating the embryoid body formation process

Issue title: Selected Presentations held at the 35th Conference of the German Society for Clinical Microcirculation and Hemorheology, Mainz, Germany, 4-5 November, 2016

Guest editors: F. Jung and T. Gori

Article type: Research Article

Authors: Xu, Xun^{a; b; 1} | Wang, Weiwei^{a; 1} | Li, Zhengdong^{a; b} | Kratz, Karl^{a; c} | Ma, Nan^{a; b; c; *} | Lendlein, Andreas^{a; b; c; *}

Affiliations: [a] Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany | [b] Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany | [c] Helmholtz Virtual Institute - Multifunctional Materials in Medicine, Berlin and Teltow, Teltow, Germany

Correspondence: [*] Corresponding author: Dr. Nan Ma and Dr. Andreas Lendlein, Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies, Helmholtz Zentrum Geesthacht, Kantstrasse 55, 14513 Teltow, Germany. Tel.: +49 3328 352 450; Fax: +49 3328 352 452; E-mails: nan.ma@hzg.de (N. Ma), andreas.lendlein@hzg.de (A. Lendlein).

Note: [1] These authors contributed equally to this work.

Abstract: The permanent loss of cardiomyocytes may lead to the irreversible damage of myocardium in cardiovascular diseases. The induced pluripotent stem cells (iPSCs) with the capacity of differentiation into a variety of cell types including cardiomyocytes showed high potential for efficient heart regeneration. The iPSCs and iPSC-derived embryoid bodies (EBs) as well as the differentiated cardiomyocytes are highly sensitive to the biophysical cues of their microenvironment, and accordingly their behavior and function can be largely modulated by microstructure of the cell culture surface. In this study, we investigated the regulatory effect of microscale roughness on both cardiomyogenesis and secretion of EBs using poly(ether imide) (PEI) cell culture inserts with different levels of bottom roughness (R0: flat surface; R1: rough surface, Rq ∼ 4 μm; R2: rough surface, Rq ∼ 23 μm). The proliferation rate and cardiomyogenesis of EBs increased with the increase of surface roughness. The EB secretome derived from R2 surface remarkably enhanced the in vitro new vessel formation of endothelial cells, as compared to those from R0 and R1. These findings highlight the potential to improve the iPSC/EB-based restoration of cardiovascular function via microstructured biomaterials.

Keywords: Microroughness, induced pluripotent stem cells, embryoid body, cardiomyogenesis, secretome

DOI: 10.3233/CH-168107

Journal: Clinical Hemorheology and Microcirculation, vol. 64, no. 3, pp. 367-382, 2016