TGFβ 1 priming enhances CXCR3-mediated mesenchymal stromal cell engraftment to the liver and enhances anti-inflammatory efficacy

• Published in: Journal of cellular and molecular medicine 2023-03, Vol.27 (6), p.864-878
• Main Authors: Garg, Abhilok, Khan, Sheeba, Luu, N, Nicholas, Davies J, Day, Victoria, King, Andrew L, Fear, Janine, Lalor, Patricia F, Newsome, Philip N
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - metabolism; Cytokines - metabolism; Humans; Liver - metabolism; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells - metabolism; Mice; Receptors, CXCR3 - metabolism
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.17698

The 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 TGβ 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 CCL murine model of liver injury treated with primed MSC. Priming of MSCs with TGFβ is a novel strategy to improve the anti-inflammatory efficacy of MSCs.