Combination human umbilical cord perivascular and endothelial colony forming cell therapy for ischemic cardiac injury

Farwah Iqbal; Alexander Johnston; Brandon Wyse; Razieh Rabani; Poonam Mander; Banafshe Hoseini; Jun Wu; Ren-Ke Li; Andrée Gauthier-Fisher; Peter Szaraz; Clifford Librach

doi:10.1038/s41536-023-00321-3

Combination human umbilical cord perivascular and endothelial colony forming cell therapy for ischemic cardiac injury

NPJ Regen Med. 2023 Aug 25;8(1):45. doi: 10.1038/s41536-023-00321-3.

Authors

Farwah Iqbal^{1

2}, Alexander Johnston¹, Brandon Wyse¹, Razieh Rabani¹, Poonam Mander¹, Banafshe Hoseini¹, Jun Wu³, Ren-Ke Li³, Andrée Gauthier-Fisher⁴, Peter Szaraz¹, Clifford Librach^{5

6

7

8}

Affiliations

¹ Create Fertility Centre, Toronto, ON, Canada.
² Virginia Tech Carillion School of Medicine, Roanoke, VA, USA.
³ Toronto General Research Institute (TGRI), University Health Network (UHN), Toronto, ON, Canada.
⁴ Create Fertility Centre, Toronto, ON, Canada. andree@createivf.com.
⁵ Create Fertility Centre, Toronto, ON, Canada. drlibrach@createivf.com.
⁶ Department of Obstetrics and Gynecology, University of Toronto, Toronto, ON, Canada. drlibrach@createivf.com.
⁷ Institute of Medical Sciences, Department of Physiology, University of Toronto, Toronto, ON, Canada. drlibrach@createivf.com.
⁸ Department of Obstetrics and Gynecology, Women's College Hospital, Toronto, ON, Canada. drlibrach@createivf.com.

Abstract

Cell-based therapeutics are promising interventions to repair ischemic cardiac tissue. However, no single cell type has yet been found to be both specialized and versatile enough to heal the heart. The synergistic effects of two regenerative cell types including endothelial colony forming cells (ECFC) and first-trimester human umbilical cord perivascular cells (FTM HUCPVC) with endothelial cell and pericyte properties respectively, on angiogenic and regenerative properties were tested in a rat model of myocardial infarction (MI), in vitro tube formation and Matrigel plug assay. The combination of FTM HUCPVCs and ECFCs synergistically reduced fibrosis and cardiomyocyte apoptosis, while promoting favorable cardiac remodeling and contractility. These effects were in part mediated by ANGPT2, PDGF-β, and VEGF-C. PDGF-β signaling-dependent synergistic effects on angiogenesis were also observed in vitro and in vivo. FTM HUCPVCs and ECFCs represent a cell combination therapy for promoting and sustaining vascularization following ischemic cardiac injury.