Local administration of porcine immunomodulatory, chemotactic and angiogenic extracellular vesicles using engineered cardiac scaffolds for myocardial infarction

The administration of extracellular vesicles (EV) from mesenchymal stromal cells (MSC) is a promising cell-free nanotherapy for tissue repair after myocardial infarction (MI). However, the optimal EV delivery strategy remains undetermined. Here, we designed a novel MSC-EV delivery, using 3D scaffolds engineered from decellularised cardiac tissue as a cell-free product for cardiac repair. EV from porcine cardiac adipose tissue-derived MSC (cATMSC) were purified by size exclusion chromatography (SEC), functionally analysed and loaded to scaffolds. cATMSC-EV markedly reduced polyclonal proliferation and pro-inflammatory cytokines production (IFN gamma, TNF alpha, IL12p40) of allogeneic PBMC. Moreover, cATMSC-EV recruited outgrowth endothelial cells (OEC) and allogeneic MSC, and promoted angiogenesis. Fluorescently labelled cATMSC-EV were mixed with peptide hydrogel, and were successfully retained in decellularised scaffolds. Then, cATMSC-EV-embedded pericardial scaffolds were administered in vivo over the ischemic myocardium in a pig model of MI. Six days from implantation, the engineered scaffold efficiently integrated into the post-infarcted myocardium. cATMSC-EV were detected within the construct and MI core, and promoted an increase in vascular density and reduction in macrophage and T cell infiltration within the damaged myocardium. The confined administration of multifunctional MSC-EV within an engineered pericardial scaffold ensures local EV dosage and release, and generates a vascularised bioactive niche for cell recruitment, engraftment and modulation of short-term post-ischemic inflammation.

Bibliographic Details

Main Authors:	Calle, Alexandra, Ramírez De Paz, Miguel Ángel, Monguio-Tortajada, Marta, Prat-Vidal, Cristina, Moron-Font, Miriam, Clos-Sansalvador, Marta, Gastelurrutia, Paloma, Cserkoova, Adriana, Morancho, Anna, Rosell, Anna, Bayes-Genis, Antoni, Galvez-Monton, Carolina, Borras, Francesc E., Roura, Santiago
Format:	artículo biblioteca
Language:	English
Published:	Springer 2021-10
Subjects:	Exosomes, Mesenchymal stem/stromal cells, Migration, Infiltration, Cardiac tissue engineering,
Online Access:	http://hdl.handle.net/20.500.12792/6146 http://hdl.handle.net/10261/289681
Tags:	Add Tag No Tags, Be the first to tag this record!