I am aware of the published studies with Fah or DPPIV knockout mice, but I am looking for an alternative to partial hepatectomy and irradiation to induce hepatocyte proliferation in wild type mice.
This is a very interesting question!
As far as I know, hepatocyte proliferation occurs mostly after liver damage, to compensate for the lost cells. This process involves a number of cytokines, which affect hepatocyte cell cycle (at least according to classic models).
It would be very interesting, if a combination of TNF-alpha and IL-6 (thought to release hepatocytes from their G0 arrest to enter G1 phase) with subsequent injection of HGF and/or EGF 12h or 24h after TNF-alpha/IL-6 injection might induce proliferation. To my knowledge only HGF or EGF injection has ever been tried.
In vitro this seems to work (see link for review on the above described topics). Though, if you wanted to try this in vivo, the dose of TNF-alpha needs to be adjusted at a low concentration to not outright kill the animals, due to induction of apoptosis.
This is just speculative, but as far as I know, nobody seems to have tried that, yet.
http://www.hindawi.com/journals/ijh/2012/689324/
Thank you Dr. Alkarim and Dr. Sowa. I agree, hepatocyte proliferation occurs in response to liver injury. I am interested to know if anyone has tried to induce it in wild type mice without any liver injury. Thanks again for your suggestions.
There is a recent report of a novel therapy which has stimulated hepatocyte proliferation in mice without hepatectomy.:
http://www.ncbi.nlm.nih.gov/pubmed/24962162
Actually, you do not need to do any pharmacological treatment for stimulating hepatocytes proliferation in vivo. The physiological method is pregnancy. After pregnancy, liver size and weight will be increase about 50% in female mice. If you want to use a nature method, you can try this one, but only female mice can be used. You can find detail information in this paper.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2822506/
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