Abstract 15067: Serum-Free Cardiac Stem Cells Provide a Superior Therapeutic Product for Clinical Translation
Cardiac stem cell (CSC) therapies represent an emerging treatment option but clinical translation is limited by the use of ill-defined culture components such as fetal bovine serum. Following previous work demonstrating that serum free xeno-free culture conditions (SF) provide a smaller product with superior functional benefits, this study examines how SF or expanded SF conditions alter the antigenic signature and differentiation potential of CSCs and the mechanism(s) underlying the salutary benefits of CSC transplant.
Methods/Results: The effects of SF conditions on the phenotypic signature of CSCs were investigated using a custom flow cytometry panel of 24 antibodies to evaluate the expression of cardiac, endothelial, hematopoietic, mesenchymal and stem cell markers. SF conditions did not alter the expression of 20 different antigens and had only minor effects on the CD29+, CD44+, CD31+ and Nestin+ content of CSCs. With the exception of a minor decline in SSEA-1+ cells (Δ1.0±0.1%, p=0.01 vs SF culture), static expansion within SF media to relevant clinical cell “doses” had negligible effects on the antigenic profile of CSCs. Flow cytometry also revealed an equivalent propensity for SF CSCs to adopt a cardiomyocyte (cTnT+; 20±1% of cells, p=0.55 vs. standard CSCs) or endothelial (vWF+; 4.3±0.5% of cells, p=0.22) lineage but reduced tendency towards a smooth muscle fate (αSMA+, 4.3±0.1% of cells, p=0.017). Despite evidence that SF CSCs provide superior functional gains when delivered to a mouse model of myocardial injury, histology showed no differences in final scar burden or vascularity. Functional improvements seen in SF treated animals were attributable to increases in viable myocardium within the infarct itself, suggesting a greater ability of SF CSCs to promote new myocardium formation within the treatment zone. Interestingly, while localized clusters of human cells positive for cTnT, vWF and αSMA were seen in all groups, SF expanded CSCs had a 0.5±0.1 fold lower tendency (p=0.03) to adopt an endothelial fate.
Conclusions: Serum-free culture and expansion of CSCs subtly alters the antigenic signature and fate of transplanted cells, increasing viable myocardium within the infarct and providing a superior cell product for clinical translation.
Author Disclosures: S. Mount: None. D.R. Davis: None.
- © 2016 by American Heart Association, Inc.