Mesenchymal stromal cells: promising treatment for liver cirrhosis

Abstract

Liver fibrosis is a wound-healing process that occurs in response to severe injuries and is hallmarked by the excessive accumulation of extracellular matrix or scar tissues within the liver. Liver fibrosis can be either acute or chronic and is induced by a variety of hepatotoxic causes, including lipid deposition, drugs, viruses, and autoimmune reactions. In advanced fibrosis, liver cirrhosis develops, a condition for which there is no successful therapy other than liver transplantation. Although liver transplantation is still a viable option, numerous limitations limit its application, including a lack of donor organs, immune rejection, and postoperative complications. As a result, there is an immediate need for a different kind of therapeutic approach. Recent research has shown that the administration of mesenchymal stromal cells (MSCs) is an attractive treatment modality for repairing liver injury and enhancing liver regeneration. This is accomplished through the cell migration into liver sites, immunoregulation, hepatogenic differentiation, as well as paracrine mechanisms. MSCs can also release a huge variety of molecules into the extracellular environment. These molecules, which include extracellular vesicles, lipids, free nucleic acids, and soluble proteins, exert crucial roles in repairing damaged tissue. In this review, we summarize the characteristics of MSCs, representative clinical study data, and the potential mechanisms of MSCs-based strategies for attenuating liver cirrhosis. Additionally, we examine the processes that are involved in the MSCs-dependent modulation of the immune milieu in liver cirrhosis. As a result, our findings lend credence to the concept of developing a cell therapy treatment for liver cirrhosis that is premised on MSCs. MSCs can be used as a candidate therapeutic agent to lengthen the survival duration of patients with liver cirrhosis or possibly reverse the condition in the near future.

Curcumin Nanofiber PCL/PLGA/Collagen Enhanced the Therapeutic Efficacy of Mesenchymal Stem Cells against Liver Fibrosis in Animal Model and Prevented its Recurrence

“…In the current study, we like to assess if curcumin preconditioning of MSCs can maintain this ameliorative effect and protect against return of the fibrosis which actually represent a critical challenge in use MSCs in therapy and still there is a controversy about the long term efficacy of stem cells, there many preclinical and clinical studies prove the reduction of liver fibrosis by MSCs injection [24][25][26] but maintaining its effect were achieved after many times of cell injection up to 9 injections in one experiment [27] and partially achieved in another studies [28][29] and not achieved at all in others [30][31]. So, we investigated the fibrosis degree on 12 th week and 24 th week of cell infusion and we found that no significant difference compared to that at 4 th week in cur + /nanoscaffold and this indicates that curcumin preconditioning of MSCs maintained the ameliorative effect of the primed MSCs and protected against the return of fibrosis compared to cur -/nanoscaffold which showed a return of fibrosis from 6.5% to 10.4% .…”

Immunomodulatory role of mesenchymal stem cell therapy in liver fibrosis

“…Producing soluble factors, including TGF-β, PGE2, IDO, NO, and HGF, MSCs were able to inhibit the activation of T cells. MSCs can induce the transdifferentiation of CD4+ T cells into CD25+Foxp3+ regulatory T cells (Tregs) through the release of TGF-β ( 7 , 49 ). Studies have demonstrated that MSCs dramatically decreased the number of CD4+ T cells invading the liver, the proportion of activated CD4+ T lymphocytes, and the total concentration of Th1 cells, and subsequently induced regulatory DCs and Tregs in the liver to ameliorate liver damage ( 65 ).…”

“…Stem cell transplantation has emerged as the most promising treatment for liver fibrosis since the advent of regenerative medicine ( 7 – 9 ). Stem cells are a population of cells with self-renewal, proliferation, and pluripotent differentiation potential that can differentiate into multiple cell types under defined conditions ( 10 , 11 ).…”

“…ESCs and iPSCs achieve therapeutic effects mainly by differentiating into mature hepatocytes in vitro or in vivo ( 8 ). MSCs, on the other hand, not only have the potential for self-renewal and differentiation ( 25 ) and can regulate the immune response ( 7 ). Moreover, since abnormal immune responses are the primary cause of liver fibrosis, MSCs are the most promising stem cells for treating liver fibrosis, as they can slow or even reverse the progression of liver fibrosis ( 26 – 28 ).…”

Co-expression of fibrotic genes in inflammatory bowel disease; A localized event?

“…Apart from IBD, fibrosis is a common complication of various diseases, such as Idiopathic Pulmonary Fibrosis (IPF) ( 6 ), Chronic Kidney Disease (CKD) ( 7 ), Systemic Sclerosis (SSc) ( 8 ) and Chronic Liver Diseases (CLD) ( 9 ) and in all cases, a successful anti-fibrotic treatment is yet to be found. Regarding intestinal fibrosis, it is most commonly symptomatic in CD rather than in UC, and in some cases, its occurrence may lead to intestinal strictures, which are amenable only to excision ( 2 ).…”