Platelets in liver regeneration

Abstract

Background and Objectives Loss of liver tissue leading to impairment of liver function represents a major cause of mortality. Understanding the mechanism of liver regeneration and developing therapies to sustain liver regeneration are of high therapeutic relevance. In this regard, platelets are considered as potential candidates for stimulating liver regeneration.Methods We aim to review the most recent evidence regarding the role of platelets in liver regeneration.Results Platelets stimulate liver regeneration in animal models of liver resection. In humans, platelets are independent predictors of postoperative mortality, liver function and volume recovery. One proposed mechanism by which platelets stimulate liver regeneration relies on their direct effect on hepatocytes. Following partial hepatectomy, platelets accumulate in the residual liver and release their granule content. Platelet-containing molecules, such as HGF, VEGF, IGF-1 and serotonin, stimulate hepatocyte proliferation. A putative additional mechanism involves the transfer of platelet mRNA to hepatocytes following platelet internalization. Recent studies have suggested that the effect of platelets relies on their interactions with LSEC. Platelets induce the secretion of IL-6 from LSEC, a strong initiator of hepatocyte proliferation. Additionally, platelets convey molecules that may impact LSEC function and, by extension, liver regeneration. Platelets potentially interact with Kupffer cells, but the effect of that interaction on liver regeneration remains to be determined.Conclusion Platelets stimulate liver regeneration. Several mechanisms seem to be involved, acting on the level of hepatocytes, LSEC and potentially Kupffer cells. Identification of the platelet-molecule(s) involved may lead to targeted therapies for patients with impairment of liver function.

Systematic review and meta-analysis of thrombocytopenia as a predictor of post-hepatectomy liver failure

“…24,27 The implication of platelets in liver regeneration recently gained considerable interest. [28][29][30] Robust data reporting the relationship between platelet count and the occurrence of PHLF in patients undergoing liver surgery is lacking, and results obtained from animal models do not necessarily reflect what takes place in humans.…”

Platelets and Platelet‐Derived Extracellular Vesicles in Liver Physiology and Disease

“…The release of granule contents during platelet activation has been suggested to trigger liver regeneration. Notably, it was suggested that platelet serotonin, vascular endothelial growth factor, HGF, and insulin like‐growth factor are involved …”

“…This has major consequences for patients with extended oncological diseases that cannot benefit from liver resection. (119,120) Platelets have been shown to contribute to liver regeneration in many ways (13)(14)(15) (Fig. 1).…”

“…Notably, it was suggested that platelet serotonin, vascular endothelial growth factor, HGF, and insulin like-growth factor are involved. (13)(14)(15) PEVs play a role in angiogenesis and endothelial regeneration. (37)(38)(39)(40)(41) PEV injection in a rat model of myocardial ischemia promoted myocardial angiogenesis.…”

“…Although the primary function of platelets is hemostasis, they also transport molecules implicated in numerous physiological processes, such as wound healing, cell activation and proliferation, angiogenesis, and immune responses . Platelet interactions with liver cells protect hepatic tissue and stimulate liver regeneration after parenchyma transection or ischemia‐reperfusion injury . However, platelets also contribute to liver injury, as detailed below …”