Abstract 723: Cortical Bone Derived Stem Cells Modulates T Cell Response After Myocardial Injury

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Rationale: The ischemic environment following myocardial infarction induces a harsh, pro-inflammatory state that facilitates the removal of necrotic tissue. Manipulation of T cell responses after cardiac injury directly impacts the outcome of the reparative response. Previous studies have demonstrated Cortical Bone Derived Stem Cells (CBSCs) improve cardiac function after myocardial infarction. CBSCs produce a diverse paracrine profile; whether this can lead to the modulation of T cell response by manipulating T cell subsets and allowing for increased cardiac wound healing post-MI remains unknown. Objective: To determine whether CBSCs secrete a paracrine profile that promotes wound healing by modulating T cell response following myocardial injury. Methods and Results: CD3+ T-lymphocytes were isolated from the spleen of C57BL/6J male mice ages 8 to 12 weeks via Fluorescent Activated Cell Sorting (FACs). CBSC secretome was introduced to T cell populations via a transwell culture system in the presence of CD3/28 coated beads with IL2. T-regulatory (Treg) populations were quantified via FACs 24 hours after in vitro CBSC exposure. Treg populations exposed to CBSC secretome in hypoxic (1% O2) conditions expanded to 26.9% of the CD4+ compartment, a 4.5 fold increase compared to control conditions. This result was further confirmed via qRT-PCR analysis. T cell culture secretome was quantified via proteome profiling of 111 soluble cytokine proteins 24 hours post CBSC exposure. CBSCs express a robust chemotaxis signature that promotes immune cell recruitment. T cells cultured in the presence of CBSC (pre-conditioned or co-culture conditions) exhibit increased CCL5, CCL22, CD40, CXCL1, and Lipocalin-2. C-reactive protein, a pro-inflammatory marker, was decreased by ~5.5 fold in the presence of CBSCs, promoting wound healing. Conclusions: CBSCs secrete a diverse paracrine profile that promotes Treg expansion during hypoxic conditions. Expansion of Treg populations post-CBSC exposure in the post-IR heart leads to increased inflammation resolution and improved myocardial wound healing, allowing for increased cardiac function and repressed cardiac remodeling.