Historical Perspectives and Advances in Mesenchymal Stem Cell Research for the Treatment of Liver Diseases

Abstract

Liver transplantation is the only effective therapy for patients with decompensated cirrhosis and fulminant liver failure. However, due to a shortage of donor livers and complications associated with immune suppression, there is an urgent need for new therapeutic strategies for patients with end-stage liver diseases. Given their unique function in self-renewal and differentiation potential, stem cells might be used to regenerate damaged liver tissue. Recent studies have shown that stem cell-based therapies can improve liver function in a mouse model of hepatic failure. Moreover, acellular liver scaffolds seeded with hepatocytes produced functional bioengineered livers for organ transplantation in preclinical studies. The therapeutic potential of stem cells or their differentiated progenies will depend on their capacity to differentiate into mature and functional cell types after transplantation. It will also be important to devise methods to overcome their genomic instability, immune reactivity, and tumorigenic potential. We review directions and advances in the use of mesenchymal stem cells and their derived hepatocytes for liver regeneration. We also discuss the potential applications of hepatocytes derived from human pluripotent stem cells and challenges to using these cells in treating end-stage liver disease.

Extracellular Vesicles Derived From Mesenchymal Stem Cells (MSC) in Regenerative Medicine: Applications in Skin Wound Healing

“…Subsequently, it was found that such cells can differentiate into different cellular types and tissues of mesenchymal origin, like bone, fat, and cartilage (Pittenger et al, 1999). Interestingly, it has been recently reported that such cells can be also induced to differentiate into cells of endodermic and ectodermic origin, like hepatocytes and neurons, respectively (Lee et al, 2018a;Marei et al, 2018).…”

Exosomes derived from human umbilical cord mesenchymal stem cells ameliorate IL-6-induced acute liver injury through miR-455-3p

“…They also secrete various growth factors and cytokines that promote cell regeneration, tissue repair, and immune regulation. MSCs have been used in mouse models for the treatment of a variety of diseases, including acute lung injury, myocardial infarction, diabetes, sepsis, liver dysfunction, and acute renal failure [4,5]. Since MSCs have shown promising clinical application prospects in animal models of human diseases, MSCbased therapies have been carried out in multiple clinical trials for the treatment of various disorders [6][7][8].…”

“…As shown on www.ClinicalTrials.gov, dozens of MSC-based clinical therapies are underway for different types of liver injury, including autoimmune hepatitis, alcoholic liver cirrhosis, and liver fibrosis. However, MSC-based therapies have been strongly limited by their unclear mechanism of action [5,9].…”

Overexpression of HNF4α enhances umbilical cord mesenchymal stem cell function to treat acute liver failure in mice through macrophage polarization

“…However, this therapy is limited by the rarity of donor livers and the poor systemic condition of patients before surgery due to long waiting time [2]. Preliminary researches indicate that stem cells play an key role in the treatment of ALF through transdifferentiating into hepatocytes to perform alternative functions, promote liver regeneration, reduce hepatocytes apoptosis, inhibit liver fibrosis, and regulate the immune and inflammatory response [3][4][5][6]. Based on importance of immune responses in ALF, the immune regulation of stem cells may be the most important factor in the treatment of ALF [7].…”