Abstract 20428: Paracrine Modulation of Cardiac Repair Processes by Cortical Bone Derived Stem Cells

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Rationale: To date cell therapy has only produced modest improvement in cardiac function, for reasons that are not yet clear. One possibility is that activation of local inflammatory response and immune cell infiltration along with release of pro-inflammatory cytokines following ischemic injury affects cardiac repair process. Cortical bone derived stem cells (CBSCs) have gained prominence due to their incredible reparative properties. Salutary effects of CBSCs in large are mediated by paracrine secretions. Since CBSCs transplantation can enhance cardiac repair processes whether CBSCs can modulate immune response is currently unknown.

Objective: Determine the therapeutic value of CBSCs in modulation of immune response after cardiac injury.

Methods and Results: CBSCs express low levels of pro-inflammatory factors in vitro. To determine whether CBSCs can modify the immune response in vivo, CBSCs were transplanted in mice after myocardial injury. Histological analysis showed reduced expression of CD86 (marker for M1 macrophage) compared to saline treated animals. Moreover, serum analysis of CBSCs animals showed significantly less expression of pro-inflammatory cytokines including TNF-α compared to saline controls as measured by cytokine profiler array. In parallel, expression of SDF-1 and MCSF was elevated in CBSCs animals. CBSCs treated animals demonstrated reduced infarct size after acute MI injury. These findings were further validated by mRNA expression analysis that showed significant reduction of pro and increased expression of anti-inflammatory factors in border zone of animals treated with CBSCs versus saline. Simultaneously, treatment of bone marrow-derived macrophages stimulated with lipopolysaccharide (LPS) or TNFα and treated with CBSCs- showed increased polarization towards M2 phenotype demonstrating immunomodulation capacity of CBSCs. Collectively, these results suggest CBSCs possess immune-modulatory properties that can enhance repair after injury.

Conclusion: CBSCs can augment cardiac repair processes by modulating the immune response after injury. Immune-modulatory properties of CBSCs highlight a potential new insight into the salutary effects of cell therapy.

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