Cell Surface Conjugation of Sialyl Lewis X Induces a Rolling Response for Mesenchymal Stem Cells
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 hom...
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| Format: | Article |
| Language: | en_US |
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Institute of Electrical and Electronics Engineers
2010
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| Online Access: | http://hdl.handle.net/1721.1/60297 |
| _version_ | 1811091300733157376 |
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| author | Karp, Jeffrey Michael Sarkar, Debanjan Spelke, Dawn P. Vemula, Praveen |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Karp, Jeffrey Michael Sarkar, Debanjan Spelke, Dawn P. Vemula, Praveen |
| author_sort | Karp, Jeffrey Michael |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:00:20Z |
| format | Article |
| id | mit-1721.1/60297 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:00:20Z |
| publishDate | 2010 |
| publisher | Institute of Electrical and Electronics Engineers |
| record_format | dspace |
| spelling | mit-1721.1/602972022-10-01T23:53:06Z Cell Surface Conjugation of Sialyl Lewis X Induces a Rolling Response for Mesenchymal Stem Cells Karp, Jeffrey Michael Sarkar, Debanjan Spelke, Dawn P. Vemula, Praveen Harvard University--MIT Division of Health Sciences and Technology Karp, Jeffrey Michael Karp, Jeffrey Michael Sarkar, Debanjan Spelke, Dawn P. Vemula, Praveen 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. 2010-12-14T21:37:39Z 2010-12-14T21:37:39Z 2009-05 2009-04 Article http://purl.org/eprint/type/ConferencePaper 978-1-4244-4362-8 INSPEC Accession Number: 10666527 http://hdl.handle.net/1721.1/60297 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. en_US http://dx.doi.org/10.1109/NEBC.2009.4967688 IEEE 35th Annual Northeast Bioengineering Conference, 2009 Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Institute of Electrical and Electronics Engineers IEEE |
| spellingShingle | Karp, Jeffrey Michael Sarkar, Debanjan Spelke, Dawn P. Vemula, Praveen Cell Surface Conjugation of Sialyl Lewis X Induces a Rolling Response for Mesenchymal Stem Cells |
| title | Cell Surface Conjugation of Sialyl Lewis X Induces a Rolling Response for Mesenchymal Stem Cells |
| title_full | Cell Surface Conjugation of Sialyl Lewis X Induces a Rolling Response for Mesenchymal Stem Cells |
| title_fullStr | Cell Surface Conjugation of Sialyl Lewis X Induces a Rolling Response for Mesenchymal Stem Cells |
| title_full_unstemmed | Cell Surface Conjugation of Sialyl Lewis X Induces a Rolling Response for Mesenchymal Stem Cells |
| title_short | Cell Surface Conjugation of Sialyl Lewis X Induces a Rolling Response for Mesenchymal Stem Cells |
| title_sort | cell surface conjugation of sialyl lewis x induces a rolling response for mesenchymal stem cells |
| url | http://hdl.handle.net/1721.1/60297 |
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