Current Therapeutic Options and Potential of Mesenchymal Stem Cell Therapy for Alcoholic Liver Disease

Abstract

Alcoholic liver disease (ALD) is a globally prevalent chronic liver disease caused by chronic or binge consumption of alcohol. The therapeutic efficiency of current therapies for ALD is limited, and there is no FDA-approved therapy for ALD at present. Various strategies targeting pathogenic events in the progression of ALD are being investigated in preclinical and clinical trials. Recently, mesenchymal stem cells (MSCs) have emerged as a promising candidate for ALD treatment and have been tested in several clinical trials. MSC-released factors have captured attention, as they have the same therapeutic function as MSCs. Herein, we focus on current therapeutic options, recently proposed strategies, and their limitations in ALD treatment. Also, we review the therapeutic effects of MSCs and those of MSC-related secretory factors on ALD. Although accumulating evidence suggests the therapeutic potential of MSCs and related factors in ALD, the mechanisms underlying their actions in ALD have not been well studied. Further investigations of the detailed mechanisms underlying the therapeutic role of MSCs in ALD are required to expand MSC therapies to clinical applications. This review provides information on current or possible treatments for ALD and contributes to our understanding of the development of effective and safe treatments for ALD.

Effect of erastin and G3139 on rat liver mitochondria in chronic alcoholic intoxication

“…Since the liver is the main barrier to toxic substances in the body, the main metabolism of ethanol occurs in it during alcohol intoxication. The metabolism of ethanol in the liver leads to formation of various hepatotoxic by-products and significant oxidative stress in the liver, and, as a result, to the death of hepatocytes [21].…”

Recent evaluation about inflammatory mechanisms in nonalcoholic fatty liver disease

“…Accumulating studies demonstrated that a pivotal issue relates to the identification of those factors that trigger inflammation, thus fuelling the transition from NAFLD to NASH ( Guo et al, 2022 ; An et al, 2023 ). These triggers of inflammtion in liver might be associated with their origins outside the liver as well as inside the organ, both of which accelerate to NASH development ( Han et al, 2022 ). Although the marked progress in unravelling the mechanism that underlie NAFLD development and progression has made, yet the elucidation of its mechanism about the pathogenesis remains limited.…”

Mi-BMSCs alleviate inflammation and fibrosis in CCl4-and TAA-induced liver cirrhosis by inhibiting TGF-β/Smad signaling

“…Extensive evidence has demonstrated that MSC-based therapy for liver cirrhosis primarily targets anti-inflammatory and anti-fibrotic effects, as well as promoting liver repair through paracrine cytokines, immune regulation, and facilitation of extracellular matrix degradation via various signaling pathways, such as TGF-β1/SMAD, Wnt/β-catenin, Ras/ERK, or Notch [ [13] , [14] , [15] , [16] , [17] , [18] ]. Presently, the transplantation of MSCs for the treatment of liver cirrhosis has been registered and its therapeutic effect has been verified in numerous clinical trials [ [19] , [20] , [21] ]. However, the main method of MSCs transplantation, peripheral intravenous injection, results in approximately 80 % of MSCs being distributed in the lungs.…”