Activation of human liver sinusoidal endothelial cell by human platelets induces hepatocyte proliferation

Abstract

Platelets promote LSEC proliferation and induce IL-6 and VEGF production. Direct contact between the platelets and LSECs and S1P, that are contained in platelets, were involved in the excretion of IL-6 from LSECs. IL-6 from LSECs induced proliferation of parenchymal hepatocytes.

Platelet Transfusion Improves Liver Function in Patients with Chronic Liver Disease and Cirrhosis

“…Platelets promote hepatocyte proliferation and have an anti-fibrotic effect in vitro (Matsuo et al 2008;Kawasaki et al 2010;Ikeda et al 2011), and thrombocytosis promotes liver regeneration and reduces liver fibrosis in vivo (Murata et al 2007;Murata et al 2008b;Myronovych et al 2008;Watanabe et al 2009). We hypothesized that platelet increment therapy would improve liver function in humans.…”

“…When the liver is injured, platelets accumulate in the injured liver and actively translocate into Disse spaces Nakamura 1992, 1993;Nakamura et al 1998;Murata et al 2007;Myronovych et al 2008). The direct contact between platelets and hepatocytes or LSECs is necessary for hepatocyte proliferation (Matsuo et al 2008;Kawasaki et al 2010), and the direct contact between platelets and HSCs is essential for an anti-fibrotic effect (Ikeda et al 2011). Taken together, the previous and current data suggest that transfused platelets delivered to the portal vein accumulate in the damaged liver due to CLD; directly contact hepatocytes, LSECs, and HSCs; and finally improve liver function and reduce liver fibrosis.…”

“…Platelets induce hepatocyte proliferation by releasing HGF and IGF-1 (Matsuo et al 2008). In addition, liver sinusoidal endothelial cells (LSECs), which constitute the sinusoidal wall, are involved in liver regeneration (Malik et al 2002), and platelets stimulate LSECs to promote hepatocyte proliferation (Kawasaki et al 2010). Thrombocytosis promotes liver regeneration not only in normal livers but also in fibrotic livers (Murata et al 2007;Murata et al 2008b;Myronovych et al 2008;Watanabe et al 2009).…”

Platelet and Liver Regeneration

“…*p < 0.05 versus S1P-group. (Reproduced from Kawasaki et al, 2010, J Hepatol with permission.) The direct contact between platelets and LSECs triggers excretion of S1P from platelets, which subsequently causes excretion of IL-6 from LSECs.…”

Evidence against a role for platelet-derived molecules in liver regeneration after partial hepatectomy in humans

“…Some studies suggest that local release of growth factors or angiogenic molecules stored within platelet alpha and dense granules are responsible for platelet-mediated liver regeneration [4,[13][14][15][16]. Even though it has been reported that platelet-derived growth factors stimulate hepatocyte proliferation in vitro [13,14,17], it has not yet been established whether platelet-derived growth factors also drive platelet-mediated liver regeneration in vivo [12]. Animal studies and a single study in humans have demonstrated accumulation of platelets within the liver remnant rapidly following a partial liver resection [5,16,18].…”