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Volume 21
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10.3390/ijms21238947
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Article

Dual Function of iPSC-Derived Pericyte-Like Cells in Vascularization and Fibrosis-Related Cardiac Tissue Remodeling In Vitro

by
Monika Szepes
1,2,
Anna Melchert
1,2,
Julia Dahlmann
1,3,
Jan Hegermann
3,4,
Christopher Werlein
5,
Danny Jonigk
2,3,5,
Axel Haverich
1,2,3,
Ulrich Martin
1,2,3,
Ruth Olmer
1,3 and
Ina Gruh
1,2,*
1
Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, Germany
2
REBIRTH—Research Center for Translational Regenerative Medicine, Hannover Medical School, 30625 Hannover, Germany
3
Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover Medical School, 30625 Hannover, Germany
4
Institute of Functional and Applied Anatomy, Research Core Unit Electron Microscopy, Hannover Medical School, 30625 Hannover, Germany
5
Institute of Pathology, Hannover Medical School, 30625 Hannover, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(23), 8947; https://doi.org/10.3390/ijms21238947
Received: 15 October 2020 / Revised: 12 November 2020 / Accepted: 20 November 2020 / Published: 25 November 2020
(This article belongs to the Special Issue Cell Programming for Cardiovascular Disease Modeling and Therapy)
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Abstract

Myocardial interstitial fibrosis (MIF) is characterized by excessive extracellular matrix (ECM) deposition, increased myocardial stiffness, functional weakening, and compensatory cardiomyocyte (CM) hypertrophy. Fibroblasts (Fbs) are considered the principal source of ECM, but the contribution of perivascular cells, including pericytes (PCs), has gained attention, since MIF develops primarily around small vessels. The pathogenesis of MIF is difficult to study in humans because of the pleiotropy of mutually influencing pathomechanisms, unpredictable side effects, and the lack of available patient samples. Human pluripotent stem cells (hPSCs) offer the unique opportunity for the de novo formation of bioartificial cardiac tissue (BCT) using a variety of different cardiovascular cell types to model aspects of MIF pathogenesis in vitro. Here, we have optimized a protocol for the derivation of hPSC-derived PC-like cells (iPSC-PCs) and present a BCT in vitro model of MIF that shows their central influence on interstitial collagen deposition and myocardial tissue stiffening. This model was used to study the interplay of different cell types—i.e., hPSC-derived CMs, endothelial cells (ECs), and iPSC-PCs or primary Fbs, respectively. While iPSC-PCs improved the sarcomere structure and supported vascularization in a PC-like fashion, the functional and histological parameters of BCTs revealed EC- and PC-mediated effects on fibrosis-related cardiac tissue remodeling. View Full-Text
Keywords: cardiac tissue engineering; iPSC-derived vascular cells; pericytes; cardiac fibroblast; myocardial interstitial fibrosis cardiac tissue engineering; iPSC-derived vascular cells; pericytes; cardiac fibroblast; myocardial interstitial fibrosis
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MDPI and ACS Style

Szepes, M.; Melchert, A.; Dahlmann, J.; Hegermann, J.; Werlein, C.; Jonigk, D.; Haverich, A.; Martin, U.; Olmer, R.; Gruh, I. Dual Function of iPSC-Derived Pericyte-Like Cells in Vascularization and Fibrosis-Related Cardiac Tissue Remodeling In Vitro. Int. J. Mol. Sci. 2020, 21, 8947. https://doi.org/10.3390/ijms21238947

AMA Style

Szepes M, Melchert A, Dahlmann J, Hegermann J, Werlein C, Jonigk D, Haverich A, Martin U, Olmer R, Gruh I. Dual Function of iPSC-Derived Pericyte-Like Cells in Vascularization and Fibrosis-Related Cardiac Tissue Remodeling In Vitro. International Journal of Molecular Sciences. 2020; 21(23):8947. https://doi.org/10.3390/ijms21238947

Chicago/Turabian Style

Szepes, Monika, Anna Melchert, Julia Dahlmann, Jan Hegermann, Christopher Werlein, Danny Jonigk, Axel Haverich, Ulrich Martin, Ruth Olmer, and Ina Gruh. 2020. "Dual Function of iPSC-Derived Pericyte-Like Cells in Vascularization and Fibrosis-Related Cardiac Tissue Remodeling In Vitro" International Journal of Molecular Sciences 21, no. 23: 8947. https://doi.org/10.3390/ijms21238947

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