Abstract 560: Surface Glycoengineering of Mesenchymal Stem Cells and Cardiosphere-Derived Cells Enhances Selectin-Mediated Cell Rolling and Tethering
Background: Of the current stem cell delivery routes, vascular injection has the advantage of not being limited by the poor vascular accessibility of the donor cells as in the cases of intramyocardial injection and cell-sheet placement. However, there is concern about the lower cell retention in the heart; thus, we access the hypothesis that modifying the cell surface glycosylation on MSCs and CDCs can enhance their interaction to inflammatory sites by increasing interactions with endothelial selectins.
Methods: Two approaches were taken to address the hypothesis. First, the non-covalent coupling of a P-selectin glycoprotein ligand-1 (PSGL-1) fusion protein called 19Fc[FUT7+] to MSCs and CDCs is performed using two types of protein G lipid conjugates, either PPG or DPG. Second, we investigated the increased of α(1,3) fucose on the cell surface glycans by overexpression of three fucosyltransferases (FUT6, FUT7, and FUT9).
Results: MSCs functionalized with 19Fc[FUT7+] were captured onto stimulated endothelial cell monolayers at wall shear stresses up to 4 dyn/cm2. Both MSCs and CDCs could be captured onto P-selectin substrates up to 6 dyn/cm2, (Table 1). In the case of fucosyltransferase overexpression, FUT7 improved the number of both MSCs and CDCs captured onto P- and E-selectin substrates. FUT9 also significantly improved the number of CDCs captured to E-selectin.
Conclusion: The current work presents a robust strategy for enabling leukocyte-like capture and rolling under constant flow conditions to enhance cell delivery efficiency thereby increasing tissue engraftment. This method could be employed to increase tissue engraftment of cells used in stem cell therapy.
Author Disclosures: C.Y. Lo: None. J.M. Canty Jr: None. S. Neelamegham: None.
This research has received full or partial funding support from the American Heart Association.
- © 2014 by American Heart Association, Inc.