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Cell Surface Conjugation of Sialyl Lewis X Induces a Rolling Response for Mesenchymal Stem Cells

Author(s)
Karp, Jeffrey Michael; Sarkar, Debanjan; Spelke, Dawn P.; Vemula, Praveen
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Abstract
There has been significant interest in the clinical use of adult mesenchymal stem cells (MSCs), which are connective tissue progenitor cells. One of the greatest challenges in traditional stem cell therapy is to deliver a large quantity of viable stem cells with high engraftment efficiency. MSCs home at a low efficiency due to the lack of relevant adhesion molecules on their surface. We have engineered the surface of the MSCs with the sialyl Lewis[superscript x] (SLeX) moiety, found on the surfaces of leukocytes representing the active site of the P-selectin glycoprotein ligand (PSGL-1) for inducing rolling response as the first step in the homing process which involves reversible, adhesive interactions between glycoprotein receptors on specific circulating cells and ligands expressed on the surface of the vascular endothelium. MSCs were covalently modified SLeX through biotin-streptavidin linkage and the rolling response of the modified MSCs were examined on P-selectin surface. Modified MSCs exhibited velocities of 2 mum/sec whereas the unmodified MSCs exhibited velocities of 65 mum/sec at a wall shear stress of 0.366 dynes/cm[superscript 2] on P-selectin surface in a parallel plate flow chamber assay. Most importantly, the MSCs' native phenotype including its ability to proliferate and differentiate into multi-lineages was retained after the modification. This platform strategy demonstrates the potential to target MSCs to specific tissues within the body by conjugation of specific targeting ligands.
Date issued
2009-05
URI
http://hdl.handle.net/1721.1/60297
Department
Harvard University--MIT Division of Health Sciences and Technology
Journal
IEEE 35th Annual Northeast Bioengineering Conference, 2009
Publisher
Institute of Electrical and Electronics Engineers
Citation
Sarkar, D. et al. “Cell surface conjugation of sialyl Lewis X induces a rolling response for mesenchymal stem cells.” Bioengineering Conference, 2009 IEEE 35th Annual Northeast. 2009. 1-2. © 2009 IEEE.
Version: Final published version
Other identifiers
INSPEC Accession Number: 10666527
ISBN
978-1-4244-4362-8

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