Engineered mesenchymal stem cells with self-assembled vesicles for systemic cell targeting
Cell therapy has the potential to impact the quality of life of suffering patients. Systemic infusion is a convenient method of cell delivery; however, the efficiency of engraftment presents a major challenge. It has been shown that modification of the cell surface with adhesion ligands is a viable...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2015
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| Online Access: | http://hdl.handle.net/1721.1/99345 https://orcid.org/0000-0003-0588-9286 |
| _version_ | 1826194974417354752 |
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| author | Sarkar, Debanjan Vemula, Praveen K. Zhao, Weian Gupta, Ashish Karnik, Rohit Karp, Jeffrey Michael |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Sarkar, Debanjan Vemula, Praveen K. Zhao, Weian Gupta, Ashish Karnik, Rohit Karp, Jeffrey Michael |
| author_sort | Sarkar, Debanjan |
| collection | MIT |
| description | Cell therapy has the potential to impact the quality of life of suffering patients. Systemic infusion is a convenient method of cell delivery; however, the efficiency of engraftment presents a major challenge. It has been shown that modification of the cell surface with adhesion ligands is a viable approach to improve cell homing, yet current methods including genetic modification suffer potential safety concerns, are practically complex and are unable to accommodate a wide variety of homing ligands or are not amendable to multiple cell types. We report herein a facile and generic approach to transiently engineer the cell surface using lipid vesicles to present biomolecular ligands that promote cell rolling, one of the first steps in the homing process. Specifically, we demonstrated that lipid vesicles rapidly fuse with the cell membrane to introduce biotin moieties on the cell surface that can subsequently conjugate streptavidin and potentially any biotinylated homing ligand. Given that cell rolling is a pre-requisite to firm adhesion for systemic cell homing, we examined the potential of immobilizing sialyl Lewis X (SLeX) on mesenchymal stem cells (MSCs) to induce cell rolling on a P-selectin surface, under dynamic flow conditions. MSCs modified with SLeX exhibit significantly improved rolling interactions with a velocity of 8 μm/s as compared to 61 μm/s for unmodified MSCs at a shear stress of 0.5 dyn/cm[superscript 2]. The cell surface modification does not impact the phenotype of the MSCs including their viability and multi-lineage differentiation potential. These results show that the transitory modification of cell surfaces with lipid vesicles can be used to efficiently immobilize adhesion ligands and potentially target systemically administered cells to the site of inflammation. |
| first_indexed | 2024-09-23T10:04:46Z |
| format | Article |
| id | mit-1721.1/99345 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:04:46Z |
| publishDate | 2015 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/993452022-09-30T18:45:55Z Engineered mesenchymal stem cells with self-assembled vesicles for systemic cell targeting Sarkar, Debanjan Vemula, Praveen K. Zhao, Weian Gupta, Ashish Karnik, Rohit Karp, Jeffrey Michael Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Mechanical Engineering Gupta, Ashish Karnik, Rohit Karp, Jeffrey Michael Cell therapy has the potential to impact the quality of life of suffering patients. Systemic infusion is a convenient method of cell delivery; however, the efficiency of engraftment presents a major challenge. It has been shown that modification of the cell surface with adhesion ligands is a viable approach to improve cell homing, yet current methods including genetic modification suffer potential safety concerns, are practically complex and are unable to accommodate a wide variety of homing ligands or are not amendable to multiple cell types. We report herein a facile and generic approach to transiently engineer the cell surface using lipid vesicles to present biomolecular ligands that promote cell rolling, one of the first steps in the homing process. Specifically, we demonstrated that lipid vesicles rapidly fuse with the cell membrane to introduce biotin moieties on the cell surface that can subsequently conjugate streptavidin and potentially any biotinylated homing ligand. Given that cell rolling is a pre-requisite to firm adhesion for systemic cell homing, we examined the potential of immobilizing sialyl Lewis X (SLeX) on mesenchymal stem cells (MSCs) to induce cell rolling on a P-selectin surface, under dynamic flow conditions. MSCs modified with SLeX exhibit significantly improved rolling interactions with a velocity of 8 μm/s as compared to 61 μm/s for unmodified MSCs at a shear stress of 0.5 dyn/cm[superscript 2]. The cell surface modification does not impact the phenotype of the MSCs including their viability and multi-lineage differentiation potential. These results show that the transitory modification of cell surfaces with lipid vesicles can be used to efficiently immobilize adhesion ligands and potentially target systemically administered cells to the site of inflammation. American Heart Association (Grant 0970178N) National Institutes of Health (U.S.) (Grant DE019191) 2015-10-15T17:27:45Z 2015-10-15T17:27:45Z 2010-04 2010-02 Article http://purl.org/eprint/type/JournalArticle 01429612 1878-5905 http://hdl.handle.net/1721.1/99345 Sarkar, Debanjan, Praveen K. Vemula, Weian Zhao, Ashish Gupta, Rohit Karnik, and Jeffrey M. Karp. “Engineered Mesenchymal Stem Cells with Self-Assembled Vesicles for Systemic Cell Targeting.” Biomaterials 31, no. 19 (July 2010): 5266–5274. https://orcid.org/0000-0003-0588-9286 en_US http://dx.doi.org/10.1016/j.biomaterials.2010.03.006 Biomaterials Creative Commons Attribution-Noncommercial-NoDerivatives http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Sarkar, Debanjan Vemula, Praveen K. Zhao, Weian Gupta, Ashish Karnik, Rohit Karp, Jeffrey Michael Engineered mesenchymal stem cells with self-assembled vesicles for systemic cell targeting |
| title | Engineered mesenchymal stem cells with self-assembled vesicles for systemic cell targeting |
| title_full | Engineered mesenchymal stem cells with self-assembled vesicles for systemic cell targeting |
| title_fullStr | Engineered mesenchymal stem cells with self-assembled vesicles for systemic cell targeting |
| title_full_unstemmed | Engineered mesenchymal stem cells with self-assembled vesicles for systemic cell targeting |
| title_short | Engineered mesenchymal stem cells with self-assembled vesicles for systemic cell targeting |
| title_sort | engineered mesenchymal stem cells with self assembled vesicles for systemic cell targeting |
| url | http://hdl.handle.net/1721.1/99345 https://orcid.org/0000-0003-0588-9286 |
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