Cell therapy: Showing cells the way home
The clinical potential of cell-based therapies is limited by poor targeting of systemically infused cells to diseased tissues. In our recent study, we have developed a multi-step screening platform to identify small molecules that boost the homing properties of mesenchymal stem cells (MSCs) to site...
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Format: | Article |
Language: | en_US |
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Impact Journals/National Center for Biotechnology Information (U.S.)
2015
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Online Access: | http://hdl.handle.net/1721.1/98484 |
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author | Heinelt, Martina Karp, Jeffrey Michael Levy, Oren |
author2 | Harvard University--MIT Division of Health Sciences and Technology |
author_facet | Harvard University--MIT Division of Health Sciences and Technology Heinelt, Martina Karp, Jeffrey Michael Levy, Oren |
author_sort | Heinelt, Martina |
collection | MIT |
description | The clinical potential of cell-based therapies is limited by poor targeting of systemically infused cells to diseased tissues. In our recent study, we have
developed a multi-step screening platform to identify small molecules that boost the homing properties of mesenchymal stem cells (MSCs) to sites of inflammation. First, a medium-throughput screen was designed to identify small molecules that upregulate surface expression of the homing integrin, cd11a (integrin αL). Ro-31-8425, a kinase inhibitor, was identified as the most potent inducer of cd11a surface expression, and was also shown to significantly increase MSC firm adhesion to the endothelial ligand of cd11a, ICAM-1, using a microfluidics-based firm adhesion assay. Finally, systemically infused Ro-31-8425-pretreated MSCs displayed improved homing to sites of inflammation and a superior anti-inflammatory impact in a murine ear inflammation model. |
first_indexed | 2024-09-23T13:25:00Z |
format | Article |
id | mit-1721.1/98484 |
institution | Massachusetts Institute of Technology |
language | en_US |
last_indexed | 2024-09-23T13:25:00Z |
publishDate | 2015 |
publisher | Impact Journals/National Center for Biotechnology Information (U.S.) |
record_format | dspace |
spelling | mit-1721.1/984842022-09-28T13:59:08Z Cell therapy: Showing cells the way home Heinelt, Martina Karp, Jeffrey Michael Levy, Oren Harvard University--MIT Division of Health Sciences and Technology Karp, Jeffrey Michael The clinical potential of cell-based therapies is limited by poor targeting of systemically infused cells to diseased tissues. In our recent study, we have developed a multi-step screening platform to identify small molecules that boost the homing properties of mesenchymal stem cells (MSCs) to sites of inflammation. First, a medium-throughput screen was designed to identify small molecules that upregulate surface expression of the homing integrin, cd11a (integrin αL). Ro-31-8425, a kinase inhibitor, was identified as the most potent inducer of cd11a surface expression, and was also shown to significantly increase MSC firm adhesion to the endothelial ligand of cd11a, ICAM-1, using a microfluidics-based firm adhesion assay. Finally, systemically infused Ro-31-8425-pretreated MSCs displayed improved homing to sites of inflammation and a superior anti-inflammatory impact in a murine ear inflammation model. 2015-09-14T18:20:52Z 2015-09-14T18:20:52Z 2015-07 2015-06 Article http://purl.org/eprint/type/JournalArticle 1949-2553 http://hdl.handle.net/1721.1/98484 Heinelt, Martina, Jeffrey M. Karp, and Oren Levy. "Cell therapy: Showing cells the way home." Oncotarget 6(20) (2015). © 2015 Impact Journals, LLC. en_US http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=4883 Oncotarget Creative Commons Attribution http://creativecommons.org/licenses/by/3.0/ application/pdf Impact Journals/National Center for Biotechnology Information (U.S.) Impact Journals/National Center for Biotechnology Information (U.S.) |
spellingShingle | Heinelt, Martina Karp, Jeffrey Michael Levy, Oren Cell therapy: Showing cells the way home |
title | Cell therapy: Showing cells the way home |
title_full | Cell therapy: Showing cells the way home |
title_fullStr | Cell therapy: Showing cells the way home |
title_full_unstemmed | Cell therapy: Showing cells the way home |
title_short | Cell therapy: Showing cells the way home |
title_sort | cell therapy showing cells the way home |
url | http://hdl.handle.net/1721.1/98484 |
work_keys_str_mv | AT heineltmartina celltherapyshowingcellsthewayhome AT karpjeffreymichael celltherapyshowingcellsthewayhome AT levyoren celltherapyshowingcellsthewayhome |