Abstract
Rationale: Adoptive transfer of multiple stem cell types into failing human hearts has demonstrated modest beneficial effects in patients with cardiovascular disorders that damage the heart. Despite increasing use of stem cell based therapies, consensus on the optimal stem cell type is still not clear. Modest repair and improvement in cardiac function in patients with cardiac complications warrants identification of a novel stem cell population that possesses enhanced proliferative capacity and can effectively survives the harsh myocardial environment. Objective: To characterize surface marker expression, proliferation, survival, migration and differentiation capacity of CBSCs relative to known and extensively studied stem cell types including MSCs and CDCs. Methods and Results: CBSCs, MSCs and CDCs were isolated from Gottingen miniswine. CBSCs possess a unique cell surface marker profile versus CDCs and MSCs. Additionally CBSCs were morphologically distinct from MSCs and CDCs and showed enhanced proliferation capacity versus CDCs and MSCs. Concurrently CBSCs had significantly increased percentage of survival after exposure to an apoptotic stimuli as compared to MSC. A significantly greater percentage of CBSCs expressed markers of cardiac lineage commitment. Additionally, CBSCs can form functional gap junction with adult ventricular myocytes. CBSCs, CDCs and MSCs showed differential response towards ATP and histamine further strengthening the differences between the three cell types. Conclusion: CBSCs have enhanced proliferative capacity and cardiac lineage commitment versus CDCs and MSCs that could account for their enhanced effects on cardiac regeneration after myocardial infarction. Ultimately, this understanding would help us to develop viable cellular therapy options for treatment of heart failure patients.
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