Cellular interactions underpinning the immunomodulatory action of mesenchymal stromal cells in models of liver transplant injury

Owen, Andrew Philip (2018). Cellular interactions underpinning the immunomodulatory action of mesenchymal stromal cells in models of liver transplant injury. University of Birmingham. Ph.D.

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Abstract

End stage liver disease represents a common end point for a number of disease processes, the only current treatment for which is liver transplantation, but the demand for donor organs exceeds the supply. This has led to the use of more marginal donors with an increase in the rates of complications. Mesenchymal stem/stromal cells (MSC) are a multipotent cell capable of modulating the immune system through a number of different processes and represent a potential therapy in post transplantation liver injury.

In this study I describe the prospective isolation and culture expansion of murine MSC. In in vitro assays MSC suppressed T lymphocytes and following stimulus with inflammatory cytokines MSC secreted a number of cytokines including Il-10. In the MDR2-/- model intravenous MSC therapy led to a reduction in liver injury with an increase in restorative macrophages. Subcutaneous administration of MSC showed no beneficial effect. MSC were also tested in a hepatic ischaemia reperfusion injury model where no effect was seen.
In summary MSC were able to suppress lymphocyte proliferation and secrete anti-inflammatory cytokines in vitro, and in vivo they were able to reduce liver injury in the MDR2-/- model but not the hepatic ischaemia reperfusion injury mode.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):