Abstract

Upon implanting tissue-engineered heart valves (TEHVs), blood-derived macrophages are believed to orchestrate the remodeling process. They initiate the immune response and mediate the remodeling of the TEHV, essential for the valve’s functionality. The exact role of another macrophage type, the tissue-resident macrophages (TRMs), has not been yet elucidated even though they maintain the homeostasis of native tissues. Here, we characterized the response of hTRM-like cells in contact with a human tissue engineered matrix (hTEM). HTEMs comprised intracellular peptides with potentially immunogenic properties in their ECM proteome. Human iPSC-derived macrophages (iMφs) could represent hTRM-like cells in vitro and circumvent the scarcity of human donor material. iMφs were derived and after stimulation they demonstrated polarization towards non-/inflammatory states. Next, they responded with increased IL-6/IL-1β secretion in separate 3/7-day cultures with longer production-time-hTEMs. We demonstrated that iMφs are a potential model for TRM-like cells for the assessment of hTEM immunocompatibility. They adopt distinct pro- and anti-inflammatory phenotypes, and both IL-6 and IL-1β secretion depends on hTEM composition. IL-6 provided the highest sensitivity to measure iMφs pro-inflammatory response. This platform could facilitate the in vitro immunocompatibility assessment of hTEMs and thereby showcase a potential way to achieve safer clinical translation of TEHVs.

Details

Title
Development of an iPSC-derived tissue-resident macrophage-based platform for the in vitro immunocompatibility assessment of human tissue engineered matrices
Author
Poulis, Nikolaos 1 ; Martin, Marcy 1 ; Hoerstrup, Simon P. 2 ; Emmert, Maximilian Y. 3 ; Fioretta, Emanuela S. 1 

 University of Zurich, Institute for Regenerative Medicine (IREM), Schlieren, Switzerland (GRID:grid.7400.3) (ISNI:0000 0004 1937 0650) 
 University of Zurich, Institute for Regenerative Medicine (IREM), Schlieren, Switzerland (GRID:grid.7400.3) (ISNI:0000 0004 1937 0650); Wyss Zurich, University and ETH Zurich, Zurich, Switzerland (GRID:grid.5801.c) (ISNI:0000 0001 2156 2780) 
 University of Zurich, Institute for Regenerative Medicine (IREM), Schlieren, Switzerland (GRID:grid.7400.3) (ISNI:0000 0004 1937 0650); Wyss Zurich, University and ETH Zurich, Zurich, Switzerland (GRID:grid.5801.c) (ISNI:0000 0001 2156 2780); Deutsches Herzzentrum der Charité (DHZC), Department of Cardiothoracic and Vascular Surgery, Berlin, Germany (GRID:grid.418209.6) (ISNI:0000 0001 0000 0404); Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany (GRID:grid.6363.0) (ISNI:0000 0001 2218 4662); University of Zurich, Institut für Regenerative Medizin (IREM), Zurich, Switzerland (GRID:grid.7400.3) (ISNI:0000 0004 1937 0650) 
Pages
12171
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3060941247
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.