FTM HUCPVCS Significantly Increase Aortic Tissue Originated Angiogenesis, Microvascular Regeneration and Cardiac Function After Myocardial Infarction

Introduction: Young perivascular tissue is a rich source of regenerative mesenchymal stem cells (MSCs) to treat severe ischemia like myocardial infarction (MI). First trimester human umbilical cord perivascular cells (FTM HUCPVCs) are novel medicinal MSCs. cGMP grade ex-vivo and in-vivo pre-clinical tests aim to develop a novel cell therapy for cardiovascular disease.
Methods: FTM HUCPVCs were expanded in cGMP (HPL-5%) condition. Rat aortic sections embedded in Matrigel™ developed endothelial networks and were co-cultured with 10k MSCs. Fox^rnu rats underwent left coronary artery ligation, FTM HUCPVCs, term HUCPVCs or BMSCs were injected locally (3x10⁶) 1week post-MI (n=8). Pressure/volume catheter tests were performed at 4 weeks after cell implantations. Scar extent, fibrotic tissue remodelling (DQ) and vascular density (IB4) were analysed.
Results: FTM HUCPVCs display MSC and pericyte identity in xeno-free conditions (CD90,CD140b,CD146>96%). FTM HUCPVCs incorporated into aortic endothelial networks and induced significantly higher network formation than older hMSCs (A). P/V readings at 4weeks after FTM HUCPVC implantation in the infarcted myocardium showed significantly higher (p<0.01) EF(%) and dPdT, and significantly lower (p<0.01) LVIDs and Tau_w compared to other treatments. Vascular density significantly increased (p<0.01,B) and ECM remodelling activity colocalized with capillaries in FTM HUCPVC treated hearts after MI. No tumor formation was observed.
Conclusion: FTM HUCPVCs provide significantly higher cardiovascular recovery both in-vitro and post-MI compared to older sources of hMSCs and promise a novel medicinal cell treatment for cardiovascular disease.

Research funded by the Government of Ontario, Canada and the Create Program Inc., Toronto, Canada