Unknown

Dataset Information

0

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

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.

SUBMITTER: Levy O 

PROVIDER: S-EPMC4361231 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

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 enable  ...[more]

Similar Datasets

Unknown Systemically Infused Mesenchymal Stem Cells Show Different Homing Profiles in Healthy and Tumor Mouse Models.
| S-EPMC5442841 | biostudies-literature
Unknown Tetrandrine identified in a small molecule screen to activate mesenchymal stem cells for enhanced immunomodulation.
| S-EPMC4960598 | biostudies-literature
Unknown An epigenetic small molecule screen to target abnormal nuclear morphology in human cells.
| S-EPMC9265153 | biostudies-literature
Unknown Identification of potent chemotypes targeting Leishmania major using a high-throughput, low-stringency, computationally enhanced, small molecule screen.
| S-EPMC2765639 | biostudies-literature
Unknown Small Molecule Screen Identifies Non-catalytic USP3 Chemical Handle.
| S-EPMC10785082 | biostudies-literature
Unknown Small-Molecule Screen Identifies De Novo Nucleotide Synthesis as a Vulnerability of Cells Lacking SIRT3.
| S-EPMC5902027 | biostudies-literature
Unknown Small molecule screen for candidate antimalarials targeting Plasmodium Kinesin-5.
| S-EPMC4047425 | biostudies-literature
Unknown Systemically administered wound-homing peptide accelerates wound healing by modulating syndecan-4 function.
| S-EPMC10700342 | biostudies-literature
Unknown Use of a small molecule integrin activator as a systemically administered vaccine adjuvant in controlling Chagas disease.
| S-EPMC8426359 | biostudies-literature
Unknown A bead-based activity screen for small-molecule inhibitors of signal transduction in chronic myelogenous leukemia cells.
| S-EPMC2868067 | biostudies-literature