Basement membrane proteins modulate cell migration on bovine pericardium extracellular matrix scaffold

Native bovine pericardium (BP) exhibits anisotropy of its surface ECM niches, with the serous surface (i.e., parietal pericardium) containing basement membrane components (e.g., Laminin, Col IV) and the fibrous surface (i.e., mediastinal side) being composed primarily of type I collagen (Col I). Native BP surface ECM niche anisotropy is preserved in antigen removed BP (AR-BP) extracellular matrix (ECM) scaffolds. By exploiting sideness (serous or fibrous surface) of AR-BP scaffolds, this study aims to determine the mechanism by which ECM niche influences human mesenchymal stem cells (hMSCs) migration. Human mesenchymal stem cells (hMSC) seeding on serous surface promoted more rapid cell migration than fibrous surface seeding. Gene analysis revealed that expression of integrin α₃ and α₁₁ were increased in cells cultured on serous surface compared to those on the fibrous side. Monoclonal antibody blockade of α₃β₁ (i.e., laminin binding) inhibited early (i.e. ≤ 6 h) hMSC migration following serous seeding, while having no effect on migration of cells on the fibrous side. Blockade of α₃β₁ resulted in decreased expression of integrin α₃ by cells on serous surface. Monoclonal antibody blockade of α₁₁β₁ (i.e., Col IV binding) inhibited serous side migration at later time points (i.e., 6-24 h). These results confirmed the role of integrin α₃β₁ binding to laminin in mediating early rapid hMSCs migration and α₁₁β₁ binding to Col IV in mediating later hMSCs migration on the serous side of AR-BP, which has critical implications for rate of cellular monolayer formation and use of AR-BP as blood contacting material for clinical applications.