Mechanism of Action

There are two main theories as to the action of stem cells in the regeneration of liver parenchyma, however, neither has been proven to be fully correct yet.

One theory postulates the trans-differentiation of BMSCs into functional hepato- cytes (Terai et al. 2003; Jang et al. 2004). The studies caused liver injury (using carbon tetrachloride [CCU) and BMSCs were transfused into the injured livers. The improvement in albumin levels indicated the functionality of the differentiated hepatocytes from the BMSCs. Both studies also noted that the effects of stem cell transplantation were only present in an injured liver when compared to uninjured controls.

The second model that has been proposed is BMSCs regenerating liver tissue through cell fusion (Wang et al. 2003; Vassilopoulos et al. 2003). It is thought that the repopulation of liver tissue is achieved by the fusion of the host and the donor cells. Vassilopoulos et al predicted that Kupffer cells from the BMSCs are the most likely candidate for fusion. These models utilised fumarylacetoacetate hydrolase (FAH) deficiency, leading to type I tyrosinaemia in mice. The FAH deficiency was achieved by lethal irradiation of the mice and FAH positive BMSCs were transplanted. Analysis of the chromosomes and alleles was the method by which fusion was confirmed.

There was uncertainty in the reporting of both models, with neither being able to rule the other out. It appeared that whilst it was agreed that both models were plausible, the authors felt that the mechanism that they proposed was the main contributor.

 
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