Department of Cardiovascular Diseases, Mayo Clinic, Stabile 4-58, 200 First Street, Rochester, MN, 55905, USA.
Sci Rep. 2021 Feb 25;11(1):4607. doi: 10.1038/s41598-021-84161-5.
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 α and α were increased in cells cultured on serous surface compared to those on the fibrous side. Monoclonal antibody blockade of αβ (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 αβ resulted in decreased expression of integrin α by cells on serous surface. Monoclonal antibody blockade of αβ (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 αβ binding to laminin in mediating early rapid hMSCs migration and αβ 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.
天然牛心包（BP）的表面细胞外基质（ECM）龛具有各向异性，浆膜面（即心外膜）含有基底膜成分（如层粘连蛋白、Col IV），而纤维面（即纵隔面）主要由 I 型胶原（Col I）组成。抗原去除 BP（AR-BP）细胞外基质（ECM）支架中保留了天然 BP 表面 ECM 龛位的各向异性。通过利用 AR-BP 支架的侧边（浆膜面或纤维面），本研究旨在确定 ECM 龛位影响人骨髓间充质干细胞（hMSC）迁移的机制。与纤维面接种相比，hMSC 在浆膜面接种可促进更快速的细胞迁移。基因分析显示，与纤维面相比，在浆膜面培养的细胞中整合素 α 和 α 的表达增加。单克隆抗体阻断αβ（即层粘连蛋白结合）抑制了 hMSC 浆膜面接种后早期（即≤6 小时）的迁移，而对纤维面细胞的迁移没有影响。αβ 阻断导致浆膜面细胞中整合素 α 的表达减少。单克隆抗体阻断αβ（即 Col IV 结合）抑制了后期（即 6-24 小时）浆膜面的迁移。这些结果证实了整合素 αβ 与层粘连蛋白结合在介导 hMSC 早期快速迁移中的作用，以及 αβ 与 Col IV 结合在介导 AR-BP 浆膜面后期 hMSC 迁移中的作用，这对细胞单层形成的速度和 AR-BP 作为临床应用中接触血液的材料的应用具有重要意义。
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