Elastomeric Cardiowrap Scaffolds Functionalized with Mesenchymal Stem Cells-Derived Exosomes Induce a Positive Modulation in the Inflammatory and Wound Healing Response of Mesenchymal Stem Cell and Macrophage.

Juan Carlos Chachques,Letizia Ferroni,Nermine Lila,Chiara Gardin,Vincenzo Gasbarro,Federica Zanotti,Veronique Migonney,Martina Trentini,Tiberio Rocca,Barbara Zavan,Celine Falentin-Daudre,Giulia Brunello

doi:10.3390/biomedicines9070824

Juan Carlos Chachques, Letizia Ferroni + Show 10 more

Open Access

https://doi.org/10.3390/biomedicines9070824

Copy DOI

Abstract

A challenge in contractile restoration of myocardial scars is one of the principal aims in cardiovascular surgery. Recently, a new potent biological tool used within healing processes is represented by exosomes derived from mesenchymal stem cells (MSCs). These cells are the well-known extracellular nanovesicles released from cells to facilitate cell function and communication. In this work, a combination of elastomeric membranes and exosomes was obtained and tested as a bioimplant. Mesenchymal stem cells (MSCs) and macrophages were seeded into the scaffold (polycaprolactone) and filled with exosomes derived from MSCs. Cells were tested for proliferation with an MTT test, and for wound healing properties and macrophage polarization by gene expression. Moreover, morphological analyses of their ability to colonize the scaffolds surfaces have been further evaluated. Results confirm that exosomes were easily entrapped onto the surface of the elastomeric scaffolds, increasing the wound healing properties and collagen type I and vitronectin of the MSC, and improving the M2 phenotype of the macrophages, mainly thanks to the increase in miRNA124 and decrease in miRNA 125. We can conclude that the enrichment of elastomeric scaffolds functionalized with exosomes is as an effective strategy to improve myocardial regeneration.

Highlights

IntroductionCardiovascular diseases (CVD) are the most worldwide cause of mortality and morbidity
The scaffold enriched with were eventually evaluated with lactate dehydrogenase (LDH) quantification, given that this test was close to damage of plasma membrane
Even preliminary and in vitro results confirm that the response of mesenchymal stem cells and macrophages are positive in terms of a morphological and molecular point of view

Summary

Introduction

Cardiovascular diseases (CVD) are the most worldwide cause of mortality and morbidity. Acute myocardial infarction and subsequent heart failure are major health issues as the human adult heart has minimal regenerative capacity [1,2]. The first biological cardiowrap strategy designed to improve systolic contraction and limit ventricular dilatation was the latissimus dorsi dynamic cardiomyoplasty (LD-CMP), which was indicated in severe heart failure patients.

Methods

Results

Discussion

Conclusion