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

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@article{1c21bcd346824499a7672431a3950646,
title = "Enhancing the adhesion of haematopoietic precursor cell integrins with hydrogen peroxide increases recruitment within murine gut",
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.",
author = "Kavanagh, {Dean P J} and Yemm, {Adrian I} and Alexander, {J Steven} and Jonathan Frampton and Neena Kalia",
year = "2013",
doi = "10.3727/096368912X653192",
language = "English",
volume = "22",
pages = "1485--1499",
journal = "Cell transplantation",
issn = "0963-6897",
publisher = "Cognizant Communication Corporation",
number = "8",

}

RIS

TY - JOUR

T1 - Enhancing the adhesion of haematopoietic precursor cell integrins with hydrogen peroxide increases recruitment within murine gut

AU - Kavanagh, Dean P J

AU - Yemm, Adrian I

AU - Alexander, J Steven

AU - Frampton, Jonathan

AU - Kalia, Neena

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

U2 - 10.3727/096368912X653192

DO - 10.3727/096368912X653192

M3 - Article

C2 - 22889470

VL - 22

SP - 1485

EP - 1499

JO - Cell transplantation

JF - Cell transplantation

SN - 0963-6897

IS - 8

ER -