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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Main Authors: Heinelt, Martina, Karp, Jeffrey Michael, Levy, Oren
Other Authors: Harvard University--MIT Division of Health Sciences and Technology
Format: Article
Language:en_US
Published: Impact Journals/National Center for Biotechnology Information (U.S.) 2015
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.
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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
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