Local delivery of cATMSC-EVs within a cardiac scaffold significantly improved right ventricle ejection fraction by 20.8% and reduced myocardial scar size and fibrosis 30 days post-myocardial infarction.
Does local delivery of cATMSC-EV via a decellularised pericardial scaffold improve cardiac function and limit remodelling in a porcine model of acute myocardial infarction?
Acellular cardiac scaffolds enriched with MSC-derived extracellular vesicles improve cardiac function, reduce fibrosis, and modulate inflammation in a preclinical porcine model of myocardial infarction.
Absolute Event Rate: 20.8% vs -6.7%
p-value: p=0.026
Rationale: Extracellular vesicles (EVs) from mesenchymal stromal cell (MSC) are a potential therapy for cardiac healing after myocardial infarction (MI).Nevertheless, neither their efficient administration nor therapeutic mechanisms are fully elucidated.Here, we evaluate the preclinical efficacy of a tissue engineering approach to locally deliver porcine cardiac adipose tissue MSC-EV (cATMSC-EV) in an acute MI pig model.Methods: After MI by permanent ligation of the coronary artery, pigs (n = 24) were randomized to Untreated or treated groups with a decellularised pericardial scaffold filled with peptide hydrogel and cATMSC-EV purified by size exclusion chromatography (EV-Treated group) or buffer (Control group), placed over the post-infarcted myocardium.Results: After 30 days, cardiac MRI showed an improved cardiac function in EV-Treated animals, with significantly higher right ventricle ejection fraction (+20.8% in EV-Treated; p = 0.026), and less ventricle dilatation, indicating less myocardial remodelling.Scar size was reduced, with less fibrosis in the distal myocardium (-42.6%Col I in EV-Treated vs Untreated; p = 0.03), a 2-fold increase in vascular density (EV-Treated; p = 0.019) and less CCL2 transcription in the infarct core.EV-treated animals had less macrophage infiltration in the infarct core (-31.7% of CD163 + cells/field in EV-Treated; p = 0.026), but 5.8 times more expressing anti-inflammatory CD73 (p = 0.015).Systemically, locally delivered cATMSC-EV also triggered a systemic effect, doubling the circulating IL-1ra (p = 0.01), and reducing the PBMC rush 2d post-MI, the TNFα and GM-CSF levels at 30d post-MI, and modulating the CD73 + and CCR2 + monocyte populations, related to immunomodulation and fibrosis modulation.Conclusions: These results highlight the potential of cATMSC-EV in modulating hallmarks of ischemic injury for cardiac repair after MI.
Prat‐Vidal et al. (2022) studied Acute myocardial infarction (n=24). cATMSC-EV delivered within a decellularised pericardial scaffold vs. Buffer in scaffold (Control) or Untreated was evaluated on Right ventricle ejection fraction (RVEF) change from baseline to 30 days (p=0.026). Local delivery of cATMSC-EVs within a cardiac scaffold significantly improved right ventricle ejection fraction by 20.8% and reduced myocardial scar size and fibrosis 30 days post-myocardial infarction.