Cell surface glycoengineering improves selectin-mediated adhesion of mesenchymal stem cells (MSCs) and cardiosphere-derived cells (CDCs): Pilot validation in porcine XXXX -reperfusion model.

@entity29547 @entity63 @entity23521 @entity4619 @entity4105 @entity8729 @entity23210 @entity1317 @entity7609
UNASSIGNED: Promising results are emerging in clinical trials focused on stem cell therapy for cardiology applications. However, the low homing and engraftment of the injected cells to target tissue continues to be a problem. Cellular glycoengineering can address this limitation by enabling the targeting of stem cells to sites of @entity1317 . Two such glycoengineering methods are presented here: i. The non-covalent incorporation of a @entity4619 ( @entity4619 ) mimetic 19Fc[ @entity23521 (+)] via lipid-protein G fusion intermediates that intercalate onto the cell surface, and ii. Over-expression of the a(1,3)fucosyltransferse @entity23521 in cells. Results demonstrate the efficient coupling of 19Fc[ @entity23521 (+)] onto both cardiosphere-derived cells (CDCs) and mesenchymal stem cells (MSCs), with coupling being more efficient when using protein G fused to single-tailed @entity7609 rather than double-tailed @entity23210 ( @entity29547 ). This non-covalent cellular modification was mild since cell proliferation and stem-cell marker expression was unaltered. Whereas coupling using 19Fc[ @entity23521 (+)] enhanced cell capture on recombinant @entity8729 or CHO-P cell surfaces, a(1,3)fucosylation was necessary for robust binding to @entity4105 and inflamed endothelial cells under shear. Pilot studies confirm the safety and homing efficacy of the modified stem cells to sites of @entity63 -reperfusion in the porcine heart. Overall, glycoengineering with physiological selectin-ligands may enhance stem cell engraftment.
