Abstract 17423: Unique Features of Cortical Bone Stem Cells Associated With Enhanced Cardiac Repair

Abstract

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 induced modest improvements in myocardial function. Recently we have shown in a mouse model that cortical bone derived stem cells (CBSCs) induced a greater enhancement of cardiac function after myocardial infarction than CDCs, possibly through enhanced paracrine signaling and transdifferentiation of the transplanted cells. However, the relative reparative potential of CBSCs relative to other known stem cell types including bone marrow derived mesenchymal stem cells (MSCs) and cardiac derived stem cells (CDCs) is not known. Objective: To characterize surface marker expression, proliferation, survival and differentiation capacity of swine CBSCs relative to MSCs and CDCs. Methods and Results: CBSCs, MSCs and CDCs were isolated from cortical bone, bone marrow and heart (left ventricle) of 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, CD44 and CD29 and are negative for CD45 and CD11-b. CBSCs had an enhanced proliferation capacity versus CPCs and MSCs, measured by CyQuant assay. Concurrently CBSCs had significantly a decreased population doubling time (3.57 and 1.26 fold decrease) as compared to MSC and CDCs respectively. CBSCs were also more hydrogen peroxide stress tolerant than CSCs and MSCs as measured by Annexin-V and propidium iodide (PI) labeling using flow cytometery. A significantly greater % of CBSCs expressed markers of cardiac lineage commitment when exposed to dexamethasone than did CSCs or MSCs. Markers of cardiac lineages including GATA-4, α SMA, Troponin T, Nkx2.5, sm22 were measured with RT-PCR and immunocytochemistry. Conclusion: CBSCs have enhanced proliferative capacity, survival in oxidative stress conditions and cardiac lineage commitment versus CSCs and MSCs. These features make them a promising cell source for cardiac regeneration after myocardial infarction.