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 (Ab(ICAM-1)), and incubated on ICAM-I coated coverslips showed a 40-fold increase in cell binding over PPG-only controls. Ab(ICAM-1)-coated MSCs incubated with human vascular endothelial cells (HUVECs), with and without exposure to TNFalpha (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 TNFalpha-treated HUVECs. Pretreatment of HUVECs with ICAM-1 antibody promoted the attachment of PPG-only MSCs while reducing the attachment of Ab(ICAM-1)-MSCs by approximately 50%. In flow chamber studies on TNFalpha-stimulated HUVECs, PPG-only, and MSC-only lost 80-90% of their initial binding at 4 dyne/cm(2), while Ab(ICAM-1)-MSCs maintained 100% binding at 4 dyne/cm(2) and 40% binding at 25 dyne/cm(2). 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.
Department of Orthopaedics, Case Western Reserve University, Cleveland, OH, USA.
In Kap
IK
Ko
Thomas J
TJ
Kean
James E
JE
Dennis
D000906:Antibodies / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007158:Immunologic Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D011485:Protein Binding; D033081:Shear Strength; D013499:Surface Properties; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1