Targeting mesenchymal stem cells to activated endothelial cells

Cell surface coating is a methodology wherein specific molecules are transiently anchored onto cell membrane to modulate cell behavior. Cell surface coating was tested as a method to deliver mesenchymal stem cells (MSCs) to endothelial cells via binding to intercellular cell adhesion molecule-1 (ICAM-1). MSCs coated with palmitated protein G (PPG) followed by antibodies to ICAM-1 (AbICAM-1), and incubated on ICAM-I coated coverslips showed a 40-fold increase in cell binding over PPG-only controls. AbICAM-1–coated MSCs incubated with human vascular endothelial cells (HUVECs), with and without exposure to TNFα (to upregulate ICAM-1 expression), showed 2.6-fold increased binding to control HUVECs over PPG-only controls, and a 16-fold increase in binding to TNFα-treated HUVECs. Pretreatment of HUVECs with ICAM-1 antibody promoted the attachment of PPG-only MSCs while reducing the attachment of AbICAM-1–MSCs by approximately 50%. In flow chamber studies on TNFα-stimulated HUVECs, PPG-only, and MSC-only lost 80–90% of their initial binding at 4 dyne/cm2, while AbICAM-1–MSCs maintained 100% binding at 4 dyne/cm2 and 40% binding at 25 dyne/cm2. These results demonstrate that cell surface coating promotes the attachment of MSCs to endothelial cells, and provides a methodology for the delivery of stem cells to sites of inflammation.