Platelet therapy: A novel strategy for liver regeneration, anti-fibrosis, and anti-apoptosis

Abstract

Platelets contain bio-physiological substances, including insulin-like growth factor-1, vascular endothelial growth factor, platelet-derived growth factor, hepatocyte growth factor, serotonin, transforming growth factor-β, adenosine diphosphate, adenosine tri-phosphate, and epidermal growth factor. Platelets have conventionally been considered to exacerbate the inflammatory response and liver injury. Recently, platelets were discovered to have a positive impact on the liver. In this review, we present experimental and clinical evidence indicating that platelets accelerate liver regeneration and have anti-fibrosis and anti-apoptosis activity, and we detail the mechanisms of action. Platelets accelerate liver regeneration by three different mechanisms: (1) a direct effect on hepatocytes, (2) a cooperative effect with liver sinusoidal endothelial cells, and (3) a collaborative effect with Kupffer cells. Platelets exert anti-fibrotic activity by deactivating hepatic stellate cells via the adenosine-cyclic adenosine 5’-monophosphate signaling pathway. Platelets prevent hepatocyte apoptosis by activating the Akt pathway and up-regulating Bcl-xL, which suppresses caspase-3 activation. Platelet therapy with thrombopoietin, thrombopoietin receptor agonists, and platelet transfusion has the advantages of convenience and cost-efficiency over other treatments. We propose that in the future, platelet therapy will play a promising role in the treatment of the various liver disorders that currently challenge the surgical field, such as liver failure after a massive hepatectomy, hepatectomy of a cirrhotic liver, and small grafts in liver transplantation.

Keywords: Platelet therapy; Liver regeneration; Liver fibrosis; Hepatocyte apoptosis; Growth factor

Core tip: Platelets have conventionally been considered to exacerbate the inflammatory response and liver injury. Recently, some studies have demonstrated a role for platelets in promoting liver regeneration, improving liver fibrosis, and attenuating hepatitis. In this review, the experimental and clinical evidence that platelets accelerate liver regeneration and attenuate fibrosis and apoptosis are described, as are the mechanisms of action. Platelet therapies, such as thrombopoietin, thrombopoietin receptor agonists, and platelet transfusion, will play a promising role in the treatment of the various liver disorders that currently challenge the surgical field.