An estimated 100 million people in the U.S. have some form of acute or chronic liver disease. Many factors, including viral and bacterial infections, substance abuse, diabetes, and fat deposition, contribute to conditions that harm the liver.

Left untreated, these liver conditions often progress to more serious diseases that often require a liver transplant. Historically, a host of issues – including a low number of tissue donors, a high rate of tissue rejection, medicine-induced immunosuppression, and high associated medical costs – has limited access to, and the effectiveness of, liver transplantation as a viable solution. 

Considering the limited options available for the successful treatment of liver disease, identifying alternative treatment options has become very important. Recently, the potential treatment of acute and chronic liver disease using regenerative medicine, also known as stem cell therapy, has garnered an increased amount of attention.

While a number of different types of stem cells have been used to treat liver disease, mesenchymal stem cells (MSCs) have been the most studied and successful in reducing the need for liver transplantation. 

MSCs have been used to repair liver tissue through a number of different methods, including co-culturing with HSCs to reduce and prevent the progression of fibrosis and the proliferation of disease-causing cells through the production and secretion of specific inflammatory factors.

Treatment of liver disease with MSCs has also been shown to increase endothelial precursor cell proliferation while suppressing apoptosis in LSECs and hepatocytes, and by lowering serum transaminase enzyme levels. MSCs have also been shown to compensate for hepatocyte reduction resulting through liver-disease induced apoptosis by differentiating into hepatocyte-like cells.  

Considering the observed role of MSCs in liver tissue repair and regeneration, Hazrati et al concluded that the use of MSCs induces the repair and regeneration of liver tissue through immune response modulation, differentiation into HLCs, increased proliferation and decreased apoptosis in hepatocytes, increased apoptosis and reduced function of HSCs and improve the function of LSECs.

The authors also point out that, as of publication, there were 61 active clinical trials using MSCs to treat a variety of liver-related diseases, including cirrhosis, fibrosis, and liver failure. The associated advantages of MSCs in the treatment of acute and chronic inflammatory liver disease include ease of isolation and culture, pluripotency, immunomodulatory and anti-inflammatory properties, extracellular signaling, and their ability to differentiate.

The authors conclude this review by summarizing the observed benefits of using MSCs, and specifically MSC-EVs to improve liver function and support the repair of damaged liver tissue. The authors also point out that while there have been numerous clinical trials using MSCs to treat liver disease, there have been no clinical trials performed on the use of MSC-EVs and call for additional research to investigate the long-term effects of treating liver disease with MSC-EVs.

Source:  “Mesenchymal Stromal/Stem Cells and Their Extracellular Vesicles ….” https://www.frontiersin.org/articles/10.3389/fimmu.2022.865888/full

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