Cardiac regeneration by pharmacologically active microcarriers releasing growth factors and/or transporting adipose-derived stem cells

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Monia Savi *
Leonardo Bocchi
Emanuela Fiumana
Caterina Frati
Francesca Bonafé
Stefano Cavalli
Paolo Giovanni Morselli
Jean-Pierre Karam
Claudia Montero-Menei
Claudio Marcello Caldarera
Carlo Guarnieri
Claudio Muscari
Donatella Stilli
Federico Quaini
Ezio Musso
(*) Corresponding Author:
Monia Savi | monia.savi@unipr.it

Abstract

We tested the hypothesis that cardiac regeneration through local delivery of adipose-derived stem cells (ASCs), activation of resident cardiac stem cells via growth factors (GFs) [hepatocyte growth factor (HGF) and insulin-like growth factor 1 (IGF-1):GFs] or both, are improved by pharmacologically active microcarriers (PAMs) interacting with cells/molecules conveyed on their surface. Rats with one-month old myocardial infarction were treated with ASCs, ASCs+PAMs, GF-releasing PAMs, ASCs+GF-releasing PAMs or vehicle. Two weeks later, hemodynamic function and inducibility of ventricular arrhythmias (VAs) were assessed. Eventually, the hearts were subjected to anatomical and immunohistochemical analyses. A significant ASCs engraftment and the largest improvement in cardiac mechanics occurred in ASC+GF-releasing PAM rats which by contrast were more vulnerable to VAs. Thus, PAMs may improve cell/GF-based cardiac regeneration although caution should be paid on the electrophysiological impact of their physical interaction with the myocardium.

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