The effects of mesenchymal stem cells on a model of autoimmune liver disease

Owen, Andrew Philip (2015). The effects of mesenchymal stem cells on a model of autoimmune liver disease. University of Birmingham. M.Res.

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Abstract

End stage liver disease is the only one of the top five causes of death in the United Kingdom increasing in prevalence each year, with the only curative treatment being liver transplantation. Autoimmune liver disease remains a prevalent but poorly understood cause with limited treatment options to prevent progression to cirrhosis. Mesenchymal stem cell (MSC) therapy is gaining an evidence base in conditions involving the immune system. This study describes a technique for prospective isolation of MSC from C57BL/6 mice and a pilot in vitro study using MSC in the OVA-Bil model of autoimmune liver injury, with the hypothesis that MSC will reduce liver inflammation.

Male 8-12 week old OVA-Bil mice were injected IP with 1x107 OT1 cells and 4x106 OT2 cells. Control mice (n=3) were given phosphate buffered saline (PBS) whilst treated mice (n=3) were infused with 5x105 PaS MSC IV on days 3 and 6. At day 10 the mice’s serum alanine transaminase (ALT) and alkaline phosphatase (ALP) were analysed. Liver tissue was fixed and paraffin sections were stained for Haematoxylin and Eosin (H&E).

No significant difference was shown in serum markers of liver injury and qualitative analysis of H&E sections demonstrated no difference in lymphocytic infiltration in the portal regions of the liver tissue between the control and MSC treated mice.

This work has demonstrated the feasibility of an in vivo animal model of autoimmune hepatitis and will guide further study into efficacy and mechanism of action of PaS MSC in models of autoimmune liver disease.

Type of Work:

Thesis (Masters by Research > M.Res.)

Award Type:

Masters by Research > M.Res.

Supervisor(s):