Abstract 31: First Trimester Human Umbilical Cord Perivascular Cells (FTM HUCPVCs) Show Superior Angiogenic Potential in Angiogenic Potency Assays When Compared to Term HUCPVCs and Bone Marrow Stromal Cells

Abstract

Introduction: Cell therapy employing pro-angiogenic cell types is a promising option for promoting revascularization of ischemic tissues. First trimester human umbilical cord perivascular cells (FTM HUCPVCs) are a young source of mesenchymal stromal cells (MSCs) that support blood vessels in the umbilical cord. Objective: We aimed to determine the angiogenic potential of FTM HUCPVCs using angiogenic potency assays and compare to older sources of MSCs: term HUCPVCs and bone marrow stromal cells (BMSCs). Methods: For the aortic ring assay, aortas were sectioned and embedded into Matrigel™. Fluorophore-labeled MSCs for testing were added to developing endothelial networks (Day0). MSC integration and network development were monitored by microscopy and quantification of endothelial networks was performed using ImageJ™ software (Day4) n=3. Using the Matrigel™ plug assay, 5.0 x10 5 MSCs were suspended with equal volumes of Matrigel™ and injected subcutaneously in 11-week-old nude mice and isolated after two weeks. Plug associated microvasculature was imaged and quantified n=3. Results: In the aortic ring assay, FTM HUCPVCs homed to endothelial networks and demonstrated greater endothelial cell coverage, when compared to term HUCPVCs and BMSCs. FTM HUCPVCs showed significantly greater network growth when compared to term HUCPVCs ( p ≤0.001), BMSCs ( p ≤0.001) and untreated endothelial networks ( p ≤0.001). FTM HUCPVC contributed to a significantly greater number of closed loops when compared to term HUCPVCs ( p ≤0.01), BMSCs ( p ≤0.001) and untreated networks ( p ≤0.05). At two weeks following injection of Matrigel plugs, FTM HUCPVC resulted in significantly greater blood vessel recruitment when compared to term HUCPVCs ( p ≤0.05), BMSCs ( p ≤0.01) and control media plugs ( p ≤0.01). Small tortuous blood vessels were found in significantly higher quantity in FTM HUCPVC injected plugs when compared to term HUCPVCs ( p ≤0.05), BMSCs (p ≤0.01) and media plugs ( p ≤0.001). Conclusions: These studies demonstrate that FTM HUCPVCs have superior potential to augment, both the initiation of capillary formation and the development of functional, perfusable blood vessels, highlighting their potential for tissue regeneration following ischemic injury.