TGFβ 1 priming enhances CXCR3-mediated mesenchymal stromal cell engraftment to the liver and enhances anti-inflammatory efficacy.
Abhilok GargSheeba KhanN LuuDavies J NicholasVictoria DayAndrew L KingJanine FearPatricia F LalorPhilip N NewsomePublished in: Journal of cellular and molecular medicine (2023)
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 1 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 4 murine model of liver injury treated with primed MSC. Priming of MSCs with TGFβ 1 is a novel strategy to improve the anti-inflammatory efficacy of MSCs.
Keyphrases
- liver injury
- drug induced
- anti inflammatory
- endothelial cells
- bone marrow
- mesenchymal stem cells
- oxidative stress
- induced pluripotent stem cells
- randomized controlled trial
- transforming growth factor
- poor prognosis
- stem cells
- systematic review
- pluripotent stem cells
- nitric oxide
- cell therapy
- single cell
- cell migration
- case control
- hematopoietic stem cell
- epithelial mesenchymal transition
- long non coding rna
- smoking cessation
- replacement therapy