Platelets promote hepatocyte proliferation in early period of liver regeneration

Platelets is likely associated with liver regeneration after hepatectomy. Using hepatocyte primary cultures in rat, we investigated the role of platelets during G1-S progression in early period of liver regeneration. Hepatocytes isolated by a collagenase perfusion method were used. Then hepatocytes were cultured in medium with/without platelets. When hepatocytes were cultured with platelets, ³H-methyl thymidine uptake was increased up to four fold in comparison to that cultured without platelets. NF-κ B and AP-1 binding activity were increased up to two or three fold in hepatocytes cultured with platelets. PCNA and cyclin D1 protein was detected only in cultured with platelets. Although it is well known that platelets contain a large amount of HGF, HGF was not detected in the medium cultured with platelets. When hepatocytes were cultured under the chamber in which platelets were seeded on the porous membrane (pore size: 0.2 μm) and soluble factors from platelets could pass through the membrane to the culture medium, ³H-methyl thymidine uptake was not increased. In electron microscopical findings platelets, which were not transformed, attached with hepatocytes and still contained granules inside. These results in this study suggest that direct touch of platelets with hepatocytes promote hepatocyte proliferation in early period of liver regeneration.