LAUSR

Introduction: Umbilical cord-derived MSC show pericyte-like characteristics and demonstrate significant angiogenic potential via paracrine and direct support to the vasculature. Endothelial progenitor cells (EPC) have the potential to initiate vascular structures while maintaining paracrine properties following ischemic injury. Hypothesis: A combination therapy of first trimester umbilical cord MSC (FTM HUCPVC) with rat EPC will promote significant angiogenesis, cardiomyocyte survival and lead to functional cardiac recovery in a rat model of MI. Methods: MI was induced by LAD ligation on 8-week-old Fox rnu rats. 1 week later, rats with notable decrease (<30%) in ejection fraction (EF) were randomly separated into 4 treatment groups (n=9) and received intramyocardial injection of: G1: Media; G2: FTM HUPVC (3х10 6 cells/rat); G3: EPC (2.2х10 6 cells/rat); G4: FTM HUCPVC - EPC combination (1:2, total cells 3х10 6 cells/rat). Endpoint analysis was at 5-days and 4-weeks after injection. Results: 5-days after injection, exclusively G4 animals showed significant cardiac recovery, improved EF and FS compared to G1 - G2 - G3 ( p <0.01). IHC analysis showed significantly less apoptosis (caspase-3), more protease activity and sarcomeric actin in combination groups G4 compared to G1-G2-G3 ( p <0.001). More FTM HUCPVC and EPC colocalized adjunct to small capillaries in G4 . Significant increase of human Angpt-2 was detected in G4 compared to G1-G2-G3 (p<0.0001). Analysis at 4-weeks post-injection showed significant improvements in end-systolic volume (128μl) and EF (43%) in G4 compared to G2 (160μl) (35%) G3 (180μl) (30%) respectively (B) . LV contractility (dpdt, tau) significantly improved in G4 compared to G1 , G2 , G3 (p<0.001). Significant reduction in scar tissue and increased LV myocardial mass was found in G4 and G2. IHC analysis showed significantly more and larger (9um) capillaries localized in LAD injured myocardium in G4 compared to G1-G2-G3 ( p <0.001). Significantly more sarcomeric actinin and connexin-43 was identified in G4 compared to G1-G2-G3 . Conclusions: Our results show the superior potential of FTM HUCPVC - EPC combination cell therapy for faster and greater cardiovascular repair and recovery compared to single-cell-type treatments for MI.