Novel Stem Cell Therapy Utilizing mRNA Technology Shows Promise in Stimulating Natural Liver Repair

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A groundbreaking stem cell therapy using mRNA technology encapsulated into nanoparticles has shown potential in regressing diseased liver tissue caused by acute or chronic liver injuries. The research, conducted by Boston Medical Center and Boston University Chobanian & Avedisian School of Medicine’s Center for Regenerative Medicine (CReM), offers a new treatment approach for end-stage liver disease, which is currently only treatable through liver transplantation.

End-stage liver disease ranks as the 12th most common cause of death in the United States. However, the critical shortage of organ donors has created a desperate need for innovative treatment options. This study explores the use of stem cells and mRNA technology to stimulate the natural repair mechanisms of the liver, potentially reducing the need for liver transplants for many patients.

The research, recently published in Cell Stem Cell, identifies a specific receptor in stem cells that can be activated by the ligand-protein vascular endothelial growth factor A (VEGFA). By targeting this receptor, the researchers aim to accelerate the conversion of biliary epithelial cells (BEC) to hepatocytes, the functional cells of the liver.

The regenerative capacity of the liver is well-known, with hepatocytes capable of proliferating to replace damaged tissue. However, chronic injury or severe hepatocyte death can exhaust this regenerative potential. To overcome this limitation, the researchers investigated the therapeutic potential of VEGFA to enhance the conversion of BECs into hepatocytes.

The researchers conducted studies using mouse and zebrafish models of liver disease. In zebrafish, liver disease was induced by genetic and chemical interventions that caused hepatocyte death. The experimental group of zebrafish was exposed to an overexpression of VEGFA, while the control group was not. The results showed a significant increase in the production of new hepatocytes from BEC-derived stem cells in the presence of VEGFA.

In mouse models, acute liver disease was induced using an overdose of acetaminophen, while chronic liver disease was promoted by a specific diet. The experimental groups were treated with two injections of VEGFA mRNA-LNP, while the control groups received neutral mRNA-LNP injections. The findings demonstrated that the delivery of VEGFA mRNA-LNP in both acute and chronic liver injuries stimulated a robust conversion of BECs into hepatocytes, with a five-fold increase compared to the control-treated mice. Notably, this treatment also led to the complete reversion of steatosis and fibrosis in the chronic model.

The therapy activates liver stem cells, a subset of biliary epithelial cells that line the liver biliary tree, causing them to proliferate and generate new healthy hepatocytes. This regenerative process holds potential for treating chronic liver diseases, allowing the liver to heal itself and potentially reducing the need for liver transplants.

One particularly significant finding from the research is the potential use of VEGFA mRNA-LNP as an alternative treatment for severe cases of acetaminophen overdose. Currently, these cases often require liver transplantation because the gold standard treatment, N-acetylcysteine (NAC), has a limited window of effectiveness. VEGFA mRNA-LNP shows promise in

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Ravina Pandya,  Content Writer, has a strong foothold in the market research industry. She specializes in writing well-researched articles from different industries, including food and beverages, information and technology, healthcare, chemical and materials, etc. With an MBA in E-commerce, she has an expertise in SEO-optimized content that resonates with industry professionals.