Mitochondrial transplantation and platelet rich plasma for the treatment of non-alcoholic fatty liver disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent global health concern, contributing to the development of insulin resistance, diabetes, cardiovascular disease, cirrhosis, and hepatocellular carcinoma. Since no approved drugs for the treatment of NAFLD exist, there is an urgent need for novel therapeutic strategies. Two such strategies are mitochondrial transplantation and platelet rich plasma (PRP) therapy. In preclinical NAFLD, mitochondrial transplantation alleviates steatosis by improving the hepatic imbalance between fatty acid utilization and synthesis. Moreover, it reduces excessive reactive oxygen species production and lipid peroxidation, thereby reducing inflammation and fibrosis. In contrast, PRP therapy ameliorates hepatic damage induced by xenobiotics by deactivating stellate cells, reducing fibrosis and apoptosis, and decreasing inflammation via NF-κB inhibition, while enhancing antioxidant defenses. These effects may be related to the improvement of NAFLD observed in a preclinical study. We propose that a combination of mitochondrial transplantation and PRP therapy may represent a novel approach for treating NAFLD by targeting different aspects of NAFLD in a complementary manner. We discuss the limitations of these therapies, as preclinical studies addressing NAFLD with these therapies are scarce, and there are no clinical trials in humans.

Keywords: Non-alcoholic fatty liver disease; Steatohepatitis; Inflammation; Cirrhosis; Oxidative stress; Electron transport chain; Tissue regeneration; Hepatocyte; Steatosis; Mitochondria

Core Tip: Liver diseases driven by mitochondrial dysfunction and oxidative stress have not yet been effectively treated, creating a need for novel therapeutic solutions. Mitochondrial transplantation restores energy metabolism, while platelet rich plasma (PRP) therapy reduces fibrosis via growth factors. This is the first review to propose the combination of mitochondrial transplantation and PRP as a novel therapeutic strategy for non-alcoholic fatty liver disease. The strategy addresses mitochondrial dysfunction, oxidative stress, and fibrosis while promoting liver regeneration, offering a promising alternative where pharmacological treatments are limited.