Integrin expression and integrin-mediated adhesion in vitro of human multipotent stromal cells (MSCs) to endothelial cells from various blood vessels

摘要

Multipotent mesenchymal stromal cells (MSCs) home to damaged tissue by processes partly regulated by integrins. Integrin subunits expressed by MSCs were identified by flow cytometry (FC), immunocytochemistry (IC), and a panel of integrin-binding antibodies. In subconfluent cultures, over 80% of MSCs expressed integrin subunits β1, β2, and α3, 20%–55% expressed α1, α2, α4, α5, α6, and αV, and about 10% expressed β3 when assayed by FC. None of the cells expressed significant levels of 13 other integrins as assayed by FC, but seven of the 13 integrins were detected by IC: β5, α7, α8, α9, α11, αX, and αD. Expression of some integrins changed with MSC confluency: integrins β3, α1, α3, α5, and αV increased, and α6 decreased. Furthermore, α4 was the only integrin to vary among preparations of MSCs from different donors. The results resolved some discrepancies in the literature concerning integrin expression by MSCs. We also investigated the role of specific integrins in MSC adhesion to endothelial cells (ECs) from the pulmonary artery (HPAEC), cardiac-derived microvasculature (HMVEC-C), and umbilical veins (HUVEC). In experiments with blocking antibodies to beta integrins, anti-β5 reduced MSC adhesion to all types of ECs, anti-β1 to both HUVEC and HPAEC, anti-β3 to HUVEC, and anti-β2 to HMVEC-C. With blocking antibodies to alpha integrins, anti-αX reduced adhesion to HPAEC and HMVEC-C, anti-αV to HPAEC, and both anti-α7 and anti-αD to HMVEC-C. Thus, MSCs use diverse integrins to adhere to EC from various blood vessels in vitro.