First trimester human umbilical cord perivascular cells (FTM HUCPVC) modulate the inflammatory response after myocardial infarction (MI) by regulating macrophage polartisation and reducing apoptosis.

Abstract

Background & Aim Introduction First trimester human umbilical cord perivascular cells (FTM HUCPVC) exhibit homing, angiogenic and tissue remodelling capacities; highlighting their potential as a novel cell therapy. This study aims to assess their use as a regenerative treatment after myocardial infarction (MI) in a small animal model. Methods, Results & Conclusion Methods FTM HUCPVC were expanded in serum (10% FBS) and cGMP compliant xeno-free (5% HPL) multilayer cultures (Corning). Immunocompromised (Foxrnu) rats (n=6) were intramyocardially injected (A) with MSC (3\u202f×\u202f106) 7 days after MI. BMSC, term HUCPVC and media injections were comparator groups. Cell localisation (Qdot labelling), ECM remodelling (DQ collagenase), infarct size (trichrome), vascularisation (IB4), contractile protein levels (SERCA and sarcomeric actinin), apoptosis (cleaved Caspase-3) and macrophage polarisation (CD68, Mannose Receptor) were assessed using immunohistochemistry. Cardiac function (echocardiography, P/V catheter and telemetry) was assessed 2 weeks, 4 weeks and 6 months post cell injection. Results FTM HUCPVC reduced infarct size (B) 4 weeks post injection (16.2±2.4, p Conclusion FTM HUCPVC induce superior functional recovery compared to older MSC sources after MI. These improvements are mediated by increased ECM remodelling, vascularity and contractile protein levels. Furthermore, FTM HUCPVC polarise macrophages to an anti-inflammatory M2 phenotype which reduces apoptosis to restore function after MI.