Unique Features of Cortical Bone Stem Cells Associated with Repair of the Injured Heart
Rationale: Adoptive transfer of multiple stem cell types has only had modest effects on the structure and function of failing human hearts. Despite increasing use of stem cell therapies, consensus on the optimal stem cell type is not adequately defined. The modest cardiac repair and functional improvement in patients with cardiac disease warrants identification of a novel stem cell population that possesses properties that induce a more substantial improvement in heart failure patients.
Objective: To characterize and compare surface marker expression, proliferation, survival, migration and differentiation capacity of Cortical Bone Stem Cells (CBSCs) relative to mesenchymal stem cells (MSCs) and cardiac derived stem cells (CDCs), that have already been tested in early stage clinical trials.
Methods and Results: CBSCs, MSCs and CDCs were isolated from Gottingen miniswine or transgenic C57/BL6 mice expressing enhanced green fluorescent protein and were expanded in-vitro. CBSCs possess a unique surface marker profile including high expression of CD61 and Integrin Beta-4 versus CDCs and MSCs. Additionally CBSCs were morphologically distinct and showed enhanced proliferation capacity versus CDCs and MSCs. CBSCs had significantly better survival after exposure to an apoptotic stimuli as compared to MSCs. ATP and histamine induced a transient increase of intracellular Ca2+ concentration in CBSCs versus CDCs and MSCs which either respond to ATP or histamine only further documenting the differences between the three cell types.
Conclusions: CBSCs are unique from CDCs and MSCs and possess enhanced proliferative, survival and lineage commitment capacity that could account for the enhanced protective effects after cardiac injury.
- Cortical bone stem cells
- cardiac repair
- immune modulation
- cardiac lineage commitment
- myocardial regeneration
- cardiac progenitor cells
- mesenchymal stem cell
- adult stem cells
- growth factors and cytokines
- Received August 6, 2015.
- Revision received October 14, 2015.
- Accepted October 15, 2015.