Targeting mesenchymal stem cells to activated endothelial cells

Area of Science:

• Biomaterials Science
• Cell Biology
• Regenerative Medicine

Background:

• Cell surface coating is a technique to modify cell membranes for specific functions.
• Mesenchymal stem cells (MSCs) are investigated for therapeutic delivery.
• Targeting endothelial cells, particularly at inflammatory sites, is crucial for effective cell delivery.

Purpose of the Study:

• To evaluate cell surface coating as a method for delivering MSCs to endothelial cells.
• To investigate the role of intercellular cell adhesion molecule-1 (ICAM-1) in this delivery process.
• To assess the efficacy of coated MSCs under flow conditions.

Main Methods:

• MSCs were coated with palmitoylated protein G (PPG) and antibodies to ICAM-1 (Ab(ICAM-1)).
• Binding assays were performed using ICAM-1 coated coverslips and human vascular endothelial cells (HUVECs), with and without TNFalpha stimulation.
• Flow chamber studies were conducted to evaluate MSC retention under shear stress.

Main Results:

• Ab(ICAM-1)-coated MSCs showed a 40-fold increase in binding to ICAM-1 coated surfaces compared to controls.
• Coated MSCs exhibited 2.6-fold increased binding to resting HUVECs and 16-fold increased binding to TNFalpha-stimulated HUVECs.
• Ab(ICAM-1)-coated MSCs maintained significantly higher binding under flow conditions (up to 25 dyne/cm(2)) compared to uncoated MSCs.

Conclusions:

• Cell surface coating effectively promotes MSC attachment to endothelial cells.
• This method enhances stem cell delivery to inflamed tissues by leveraging ICAM-1 expression.
• Cell surface coating offers a promising strategy for targeted stem cell therapy.