Abstract 13083: Cocooning of Cardiac Stem Cells Within Hydrogel Microcapsules Supplemented With Integrin-binding Proteins Promotes Cell Survival and Post Ischemic Cardiac Function
Transplantation of ex vivo proliferated cardiac stem cells (CSCs) is an emerging therapy for ischemic cardiomyopathy but several studies have shown that CSC-mediated cardiac repair is limited by poor engraftment and survival. Therefore, we explored the effect of single-cell microencapsulation to increase CSCs survival and engraftment after myocardial injection.
Methods/Results: CSCs were cultured from atrial appendage biopsies obtained from patients undergoing clinically-indicated surgery. Screening of CSCs for expression of surface integrins demonstrated that α2-7, α11, αD, αE, αL, αV, αX and β1-8 were significantly expressed. Western blots confirmed strong expression of the pro-survival integrin dimers αVβ3 and α5β1; thus rationalizing the use fibronectin and fibrinogen as a supportive matrix for human CSCs. Encapsulation increased CSC viability when compared to cells in suspension culture or unsupplemented capsules (1.4±0.1 vs. -0.9±0.1 or 1.0±0.1 fold change in cell numbers over 24 hours, respectively; p≤0.05). Encapsulation maintained stable expression of Jun, Fos and Bcl-2 (p≥0.2 compared to adherent culture) while survival in suspension conditions mandated adaptive increases in transcript expression to survive loss of integrin attachments (p≤0.05). When compared to conditioned media (CM) from suspended CSCs, CM from encapsulated CSCs provided: 1) superior production of the pro-angiogenic/cardioprotective cytokines angiogenin and SDF-1α, 2) enhanced blood vessel formation in a standard cytokine-depleted matrigel assay and 3) superior recruitment of circulating resident stem cells. Injection of encapsulated human CSCs into immunodeficient mice one week after experimental myocardial infarction increased cell retention by 2.1±0.6 fold (p≤0.05 vs. standard vehicle) while boosting CSC-mediated cardiac repair as compared to non-encapsulated CSCs.
Conclusions: Encapsulation of CSCs in supplemented hydrogel enhanced survival, angiogenic capacity, cytokine release and stem cell recruitment by restoring vital attachment cues that prevent detachment induced apoptosis. Single cell encapsulation boosts retention and the functional benefits seen after transplantation of human CSCs into damaged myocardium.
- © 2013 by American Heart Association, Inc.