TGFβ1 priming enhances CXCR3‐mediated mesenchymal stromal cell engraftment to the liver and enhances anti‐inflammatory efficacy

Author:

Garg Abhilok12,Khan Sheeba12ORCID,Luu N.12,Nicholas Davies J.12,Day Victoria12,King Andrew L.12,Fear Janine12,Lalor Patricia F.12,Newsome Philip N.123

Affiliation:

1. National Institute for Health Research Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust University of Birmingham Birmingham UK

2. Centre for Liver & Gastrointestinal Research, Institute of Immunology and Immunotherapy University of Birmingham Birmingham UK

3. Liver Unit University Hospitals Birmingham NHS Foundation Trust Birmingham UK

Abstract

AbstractThe immunomodulatory characteristics of mesenchymal stromal cells (MSC) confers them with potential therapeutic value in the treatment of inflammatory/immune‐mediated conditions. Previous studies have reported only modest beneficial effects in murine models of liver injury. In our study we explored the role of MSC priming to enhance their effectiveness. Herein we demonstrate that stimulation of human MSC with cytokine TGβ1 enhances their homing and engraftment to human and murine hepatic sinusoidal endothelium in vivo and in vitro, which was mediated by increased expression of CXCR3. Alongside improved hepatic homing there was also greater reduction in liver inflammation and necrosis, with no adverse effects, in the CCL4 murine model of liver injury treated with primed MSC. Priming of MSCs with TGFβ1 is a novel strategy to improve the anti‐inflammatory efficacy of MSCs.

Publisher

Wiley

Subject

Cell Biology,Molecular Medicine

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