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Summary Platelets are involved in the early phases of liver regeneration. Moreover, platelet transfusion and thrombocytosis were recently shown to enhance hepatocyte proliferation. However, the precise mechanisms remain elusive. This review discusses the latest updates regarding the mechanisms by which platelets stimulate liver regeneration, focusing on their interactions with liver sinusoidal endothelial cells and on their fate within the liver. Following liver injury, platelets are recruited to and trapped within the liver, where they adhere to the endothelium. Subsequent platelet activation results in the release of platelet granules, which stimulate hepatocyte proliferation through activation of the Akt and ERK1/2 signalling pathways. Platelets activate liver sinusoidal endothelial cells, leading to the secretion of growth factors, such as interleukin-6. Finally, liver sinusoidal cells and hepatocytes can also internalize platelets, but the effects of this alternate process on liver regeneration remain to be explored. A better understanding of the mechanisms by which platelets stimulate liver regeneration could lead to improvement in post-operative organ function and allow hepatectomies of a greater extent to be performed. [ABSTRACT FROM AUTHOR]

Background & Aims Mesenchymal stem cell (MSC) transplantation was shown to be effective for the treatment of liver fibrosis, but the mechanisms of action are not yet fully understood. We transplanted encapsulated human MSCs in two mouse models of liver fibrosis to determine the mechanisms behind the protective effect. Methods Human bone marrow-derived MSCs were microencapsulated in novel alginate-polyethylene glycol microspheres. In vitro , we analyzed the effect of MSC-conditioned medium on the activation of hepatic stellate cells and the viability, proliferation, cytokine secretion, and differentiation capacity of encapsulated MSCs. The level of fibrosis induced by bile duct ligation (BDL) or carbon tetrachloride (CCl 4 ) was assessed after intraperitoneal transplantation of encapsulated MSCs, encapsulated human fibroblasts, and empty microspheres. Results MSC-conditioned medium inhibited hepatic stellate cell activation and release of MSC secreted anti-apoptotic (IL-6, IGFBP-2) and anti-inflammatory (IL-1Ra) cytokines. Viability, proliferation, and cytokine secretion of microencapsulated MSCs were similar to those of non-encapsulated MSCs. Within the microspheres, MSCs maintained their capacity to differentiate into adipocytes, chondrocytes, and osteocytes. 23% (5/22) of the MSC clones were able to produce anti-inflammatory IL-1Ra in vitro . Microencapsulated MSCs significantly delayed the development of BDL- and CCl 4 -induced liver fibrosis. Fibroblasts had an intermediate effect against CCl 4 -induced fibrosis. Mice transplanted with encapsulated MSCs showed lower mRNA levels of collagen type I, whereas levels of matrix metalloproteinase 9 were significantly higher. Human IL-1Ra was detected in the serum of 36% (4/11) of the mice transplanted with microencapsulated MSCs. Conclusions MSC-derived soluble molecules are responsible for an anti-fibrotic effect in experimental liver fibrosis. [ABSTRACT FROM AUTHOR]