Enhancing the adhesion of haematopoietic precursor cell integrins with hydrogen peroxide increases recruitment within murine gut

Research output: Contribution to journalArticle

Abstract

Hematopoietic stem cells (HSCs) migrate to injury sites and aid in tissue repair. However, clinical success is poor and is partially due to limited HSC recruitment. We hypothesized that HSC pre-treatment with H₂O₂ would enhance their recruitment to injured gut. As HSCs are rare cells, the number of primary cells obtained from donors is often inadequate for functional experiments. To circumvent this, in this study we utilized a functionally relevant cell line, HPC-7. Anaesthetised mice were subjected to intestinal ischemia-reperfusion (IR) injury and HPC-7 recruitment was examined intravitally. Adhesion to endothelial cells (ECs), injured gut sections and ICAM-1/VCAM-1 protein was also quantitated in vitro. H₂O₂ pre-treatment significantly enhanced HPC-7 recruitment to injured gut in vivo. A concomitant reduction in pulmonary adhesion was also observed. Enhanced adhesion was also observed in all in vitro models. Increased clustering of α ₄ and β ₂ integrins, F-actin polymerisation and filopodia formation was observed in pre-treated HPC-7s. Importantly, H₂O₂ did not reduce HPC-7 viability or proliferative ability. HPC-7 recruitment to injured gut can be modulated by H₂O₂ pre-treatment. This may be through increasing the affinity or avidity of surface integrins that mediate HPC-7 homing to injured sites, or through stimulating the migratory apparatus. Strategies that enhance hematopoietic stem/progenitor cell recruitment may ultimately affect their therapeutic efficacy.

Details

Original languageEnglish
Pages (from-to)1485-1499
Number of pages15
JournalCell transplantation
Volume22
Issue number8
Publication statusPublished - 2013