Abstract 157: Unique Features of Cortical Bone Stem Cells Associated With Enhanced Cardiac Repair
Rationale: Adoptive transfer of bone marrow and cardiac derived stem cells (CDCs) into failing human hearts has been shown to be safe, yet these cells have only induced modest improvements after myocardial infarction (MI). Recently we have shown in a mouse model that cortical bone derived stem cells (CBSCs) induced a greater enhancement of cardiac function after MI through enhanced paracrine signaling and transdifferentiation of CBSCs into new cardiac tissue. However, the reparative potential of CBSCs relative to other stem cell types including bone marrow derived mesenchymal stem cells (MSCs) and CDCs is not known.
Objective: To characterize surface marker expression, proliferation, survival, migration and differentiation capacity of swine CBSCs relative to MSCs and CDCs.
Methods and Results: CBSCs, MSCs and CDCs were isolated from Gottingen miniswine. CBSCs were morphologically distinct from MSCs and CDCs, with differences in length to width ratio and overall cell surface area. Cell surface marker profiling using RT-PCR analysis revealed that CBSCs express some of the classical MSC markers such as CD106, CD271, CD105, CD90 and CD29 and are negative for CD45 and CD11-b. CBSCs had an enhanced proliferation capacity versus CDCs and MSCs, measured by CyQuant assay. Concurrently CBSCs had significantly decreased population-doubling time (3.57 and 1.26 fold decrease) as compared to MSC and CDCs. CBSCs exhibit enhanced survival after exposure to apoptotic stimuli as compared to MSCs measured by Annexin-V staining. A significantly greater % of CBSCs expressed markers of cardiac lineage commitment when exposed to dexamethasone than did CDCs or MSCs. Markers of cardiac lineages including GATA-4, α SMA, Troponin T, sm22 were measured with RT-PCR and immunocytochemistry.
Conclusion: CBSCs have enhanced proliferative, survival capacity and cardiac lineage commitment versus CDCs and MSCs that could account for their enhanced effects on cardiac regeneration after myocardial infarction.
Author Disclosures: S. Mohsin: None. C.D. Troupes: None. T.E. Sharp: None. T. Starosta: None. E.J. Agra: None. S. Smith: None. H. Kubo: None. R.M. Berretta: None. S.R. Houser: None.
- © 2015 by American Heart Association, Inc.