A small-molecule screen for enhanced homing of systemically infused cells

Cell Reports
Oren LevyJeffrey M Karp

Abstract

Poor homing of systemically infused cells to disease sites may limit the success of exogenous cell-based therapy. In this study, we screened 9,000 signal-transduction modulators to identify hits that increase mesenchymal stromal cell (MSC) surface expression of homing ligands that bind to intercellular adhesion molecule 1 (ICAM-1), such as CD11a. Pretreatment of MSCs with Ro-31-8425, an identified hit from this screen, increased MSC firm adhesion to an ICAM-1-coated substrate in vitro and enabled targeted delivery of systemically administered MSCs to inflamed sites in vivo in a CD11a- (and other ICAM-1-binding domains)-dependent manner. This resulted in a heightened anti-inflammatory response. This represents a new strategy for engineering cell homing to enhance therapeutic efficacy and validates CD11a and ICAM-1 as potential targets. Altogether, this multi-step screening process may significantly improve clinical outcomes of cell-based therapies.

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Citations

Jun 29, 2016·Stem Cells·Tyler A AllenKe Cheng
Mar 21, 2017·Stem Cells·Franziska NitzscheJohannes Boltze
Aug 3, 2017·Journal of Cellular and Molecular Medicine·Xuan LiFa-Ming Chen
Aug 3, 2018·Stem Cells Translational Medicine·Timothy E G KruegerW Nathaniel Brennen
May 31, 2017·Human Gene Therapy·Francesco Albert Bosco CorteseGiovanni Santostasi
May 3, 2019·Stem Cell Research & Therapy·Nádia de Cássia NoronhaKelen C R Malmegrim
Mar 11, 2017·Stem Cell Research & Therapy·Simone PacioniRoberto Pallini
Aug 11, 2015·Oncotarget·Martina HeineltOren Levy
Dec 10, 2019·Npj Regenerative Medicine·Mark F PittengerArnold I Caplan
Apr 5, 2019·Nature Biomedical Engineering·James Q YinJames A Ankrum
Jul 9, 2020·International Journal of Molecular Sciences·Catharina MelzerRalf Hass
Jan 6, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Oren LevyJeffrey M Karp
Feb 18, 2021·Advanced Healthcare Materials·Marissa E WechslerKristi S Anseth
Mar 9, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·David Pozo
Jun 18, 2021·Stem Cell Reviews and Reports·Alison R Mercer-SmithShawn D Hingtgen

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