Applications of Mesenchymal Stem Cells in Liver Fibrosis: Novel Strategies, Mechanisms, and Clinical Practice

Abstract

Liver fibrosis is a common result of most chronic liver diseases, and advanced fibrosis often leads to cirrhosis. Currently, there is no effective treatment for liver cirrhosis except liver transplantation. Therefore, it is important to carry out antifibrosis treatment to reverse liver damage in the early stage of liver fibrosis. Mesenchymal stem cells (MSCs) are the most widely used stem cells in the field of regenerative medicine. The preclinical and clinical research results of MSCs in the treatment of liver fibrosis and cirrhosis show that MSC administration is a promising treatment for liver fibrosis and cirrhosis. MSCs reverse liver fibrosis and increase liver function mainly through differentiation into hepatocytes, immune regulation, secretion of cytokines and other nutritional factors, reduction of hepatocyte apoptosis, and promotion of hepatocyte regeneration. Recently, many studies provided a variety of new methods and strategies to improve the effect of MSCs in the treatment of liver fibrosis. In this review, we summarized the current effective methods and strategies and their potential mechanisms of MSCs in the treatment of liver fibrosis, as well as the current research progress in clinical practice. We expect to achieve complete reversal of liver injury with MSC-based therapy in the future.

Mesenchymal Stem Cell-Derived Exosomes as a Novel Strategy for the Treatment of Intervertebral Disc Degeneration

“…Actually, mesenchymal stem cells (MSCs) have shown safety as well as therapeutic significance in the field of regenerative medicine ( Mocchi et al, 2020 ). Currently, about 1,000 clinical trials worldwide have been reported to use MSCs to treat various diseases ( Pittenger et al, 2019 ; Kabat et al, 2020 ), including inflammatory and fibrotic diseases ( Ryu et al, 2020 ); liver disease ( Zhu et al, 2021 ), bone and joint diseases ( Li N. et al, 2020 ), inflammatory bowel diseases ( Zhang X. et al, 2020 ), diabetes ( Kuang et al, 2021 ), cardiovascular diseases ( Chen et al, 2021 ), neurodegenerative diseases ( Fayazi et al, 2021 ), spinal cord injuries ( Huang et al, 2021 ) and so on. Likewise, the emergence of cell-based therapies has also paved the way for utilizing MSCs in IVDD treatment.…”

“…Previous studies showed that the co-culture of MSCs with nucleus pulposus cells not only stimulated the NPCs proliferation but also attenuated cell apoptosis in the degenerated IVD. Studies have shown that exosomes derived from MSC replicate these therapeutic effects of their parent cells ( Faruqu et al, 2021 ; Zhu et al, 2021 ). For in vitro disc degeneration model induced by different biochemical challenges, including H 2 O 2 , LPS, IL-1β, TNF-ɑ, acidic pH, and high glucose, the administration of MSC-derived exosomes exerts pro-proliferation and anti-apoptosis effect via distinct mechanisms.…”

Mesenchymal Stem Cells Influence Activation of Hepatic Stellate Cells, and Constitute a Promising Therapy for Liver Fibrosis

“…Fifty-six clinical trials using MSCs for liver disease, such as cirrhosis, acute liver failure, and hepatitis, have been reported and the majority of these were registered in Asian countries [ 117 ]. MSCs that are mostly obtained from bone marrow, umbilical cord, and adipose tissue are used in clinical trials of the liver, and injected through the peripheral vein or the hepatic artery [ 118 ]. The number of cells and frequency of injection varies, and the MSC effect on liver fibrosis is inconsistent.…”

Hypoxia-stimulated mesenchymal stem cell-derived exosomes loaded by adhesive hydrogel for effective angiogenic treatment of spinal cord injury

“…Mesenchymal stem cells (MSCs) have already been documented to possess angiogenic capacity as well as anti-apoptotic and immunomodulatory effects, which benefit the treatment of numerous diseases. [7][8][9] Interestingly, recent studies have revealed that the therapeutic effects of MSCs are mainly contributed from cellular paracrine mechanisms. [10][11][12] As extracellular vesicles, exosomes play an essential role in intercellular communication and cargo transportation, including ribonucleic acid (RNA), enzymes, cytokines, etc.…”