In-Situ Myocardial Tissue Engineering Inspired by Matricellular Protein

The human heart has a minimal capacity to regenerate heart muscle cells, and any significant loss leads to heart failure. A classical paradigm in regenerative medicine is to induce tissue regeneration and repair by the transplantation of cells alone, or cells combined with biomaterial scaffolds. An alternative strategy is to harness the latent regenerative potential of the host tissue by mobilizing, recruiting, and stimulating cell populations in situ via signaling cues - in-situ regeneration.

Osteopontin (OPN) is a secreted matricellular cytokine that signals through integrin and CD44 receptors. Osteopontin (OPN) is upregulated after tissue injury. Our preliminary studies suggest that macrophage-secreted OPN plays a role in myocardial regeneration in neonatal heart. OPN stimulates cell-cycle activity in neonatal cardiomyocytes through YAP1 activity. Acute treatment of OPN improved cardiac remodeling and function after myocardial infarction in the mouse.

In summary, we identified, for the first time, the reparative properties of OPN in myocardial regeneration and repair. Our findings are significant because OPN can be used as a regenerative therapy to treat acute myocardial infarction to prevent adverse cardiac remodeling and heart failure.