Abstract 13374: Enhancing Myocardial Repair with CardioChimeras
Transplantation of cardiac progenitor cells (CPCs) and mesenchymal stem cells (MSCs) after infarction support modest improvements in cardiac function, however there are currently no reports substantiating a single stem cell type supporting both direct and indirect mechanisms of repair. Therefore, we created a CardioChimera (CC), a progenitor cell formed by fusion between CPCs and MSCs, resulting in a unique progeny superior to either individual precursor. CardioChimeras are mono-nucleated, have unique growth kinetics and do not display increases in cell death relative to parental CPCs and MSCs. CCs have increased cellular size unrelated to cell cycle arrest and/or senescence based on mRNA analysis of p16 and p53. As proof of principle, CCs co-cultured with serum starved cardiomyocytes blunted myocyte cell death (2-fold) relative to parent cells and increased myocyte size not observed with co-culture of CPCs alone. CCs enhance myocyte growth similar to parent MSCs owing to an increased propensity to secrete pro-survival and anti-inflammatory factors FGF2 (2.5-fold) and Il-6 (17.5-fold). CCs upregulate markers of cardiogenic commitment after co-culture with cardiomyocytes as represented by mRNA for cardiac troponin T (6-fold) and CD31 (6-fold). CardioChimera 1 (CC1) injection after myocardial infarction (MI) improves Left Ventricular (LV) anterior wall thickness at 4 weeks (p<0.01) and 8 weeks (p<0.001) after MI relative to PBS (no cell treatment) hearts and CC1 hearts are indistinguishable from sham controls at 4 weeks after damage. Additionally, both CC1 and CardioChimera 3 (CC3) treatment increases the amount of viable LV mass 8 weeks after MI compared to PBS hearts (p<0.05). Ejection fraction was enhanced by 20% in CC1 and CC3 treated hearts at 3 weeks (p<0.001 and p<0.001 respectively), which sustains up to 8 weeks in CC1 (p<0.001) and CC3 hearts (p<0.01). Collectively, CCs represent an adaptable cell therapy combining the beneficial properties of CPCs to undergo cardiac specific commitment as well as MSCs to foster an improved microenvironment with protective paracrine secretion. CCs merge the application of distinct cell types into a single entity for blunting the progression of heart failure and promoting myocardial regeneration.
- Stem cell therapy
- Regenerative medicine stem cells
- Myocardial infarction
- Cardiac regeneration
- Growth factors
Author Disclosures: P.J. Quijada: None. H.T. Salunga: None. J. Cubillo: None. J. Emathinger: None. M.A. Sussman: None.
- © 2014 by American Heart Association, Inc.