Mesenchymal stem cell-based cell-free strategies: safe and effective treatments for liver injury

Hu, Chenxia; Zhao, Lingfei; Zhang, Lingjian; Bao, Qiongling

doi:10.1186/s13287-020-01895-1

Cited by 99 publications

(59 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Mesenchymal stem cells (MSCs) have a self-renewal capacity and are derived from the bone marrow, adipose tissue, umbilical cord, etc. They are the subject of focus in regenerative medicine and serve as a potential therapy for different liver diseases[ 151 , 152 ]. MSCs were shown to improve liver regeneration in patients with cirrhosis by elevating anti-apoptotic factors, such as HGF and IGF-1, and angiogenic and mitogenic factors.…”

Section: Stimulation Of Insufficient Liver Regenerationmentioning

confidence: 99%

Molecular pathways of liver regeneration: A comprehensive review

Kiseleva¹,

Antonyan²,

Zharikova³

et al. 2021

WJH

View full text Add to dashboard Cite

The liver is a unique parenchymal organ with a regenerative capacity allowing it to restore up to 70% of its volume. Although knowledge of this phenomenon dates back to Greek mythology (the story of Prometheus), many aspects of liver regeneration are still not understood. A variety of different factors, including inflammatory cytokines, growth factors, and bile acids, promote liver regeneration and control the final size of the organ during typical regeneration, which is performed by mature hepatocytes, and during alternative regeneration, which is performed by recently identified resident stem cells called “hepatic progenitor cells”. Hepatic progenitor cells drive liver regeneration when hepatocytes are unable to restore the liver mass, such as in cases of chronic injury or excessive acute injury. In liver maintenance, the body mass ratio is essential for homeostasis because the liver has numerous functions; therefore, a greater understanding of this process will lead to better control of liver injuries, improved transplantation of small grafts and the discovery of new methods for the treatment of liver diseases. The current review sheds light on the key molecular pathways and cells involved in typical and progenitor-dependent liver mass regeneration after various acute or chronic injuries. Subsequent studies and a better understanding of liver regeneration will lead to the development of new therapeutic methods for liver diseases.

show abstract

Section: Stimulation Of Insufficient Liver Regenerationmentioning

confidence: 99%

Molecular pathways of liver regeneration: A comprehensive review

Kiseleva¹,

Antonyan²,

Zharikova³

et al. 2021

WJH

View full text Add to dashboard Cite

show abstract

“…In vitro and in vivo experiments demonstrated that MSCs mainly exert antifibrotic effects by paracrine mechanisms (70). Secretomes or the culture medium of MSCs could also significantly suppress liver fibrosis (71). MSC transplantation could alleviate liver fibrosis and reduce the expression of transforming growth factor-β1 (TGF-β1), Smad2, collagen type I, and α-SMA, and pathological examination showed reduced liver fibrosis areas (72) On the other hand, MSCs can regulate the EMT-MET balance in fibrogenic liver tissue.…”

Section: Mechanism Of the Antifibrotic Effect Of Mscmentioning

confidence: 99%

The Application of Mesenchymal Stem Cells in the Treatment of Liver Diseases: Mechanism, Efficacy, and Safety Issues

et al. 2021

Self Cite

View full text Add to dashboard Cite

Mesenchymal stem cell (MSC) transplantation is a novel treatment for liver diseases due to the roles of MSCs in regeneration, fibrosis inhibition and immune regulation. However, the mechanisms are still not completely understood. Despite the significant efficacy of MSC therapy in animal models and preliminary clinical trials, issues remain. The efficacy and safety of MSC-based therapy in the treatment of liver diseases remains a challenging issue that requires more investigation. This article reviews recent studies on the mechanisms of MSCs in liver diseases and the associated challenges and suggests potential future applications.

show abstract

“…The most effective treatment for end-stage liver disease is orthotopic liver transplantation (OLT). However, its application is limited due to the shortage of organ donors, the high cost and immunosuppression [3,4].…”

Section: Introductionmentioning

confidence: 99%

The adipose-derived mesenchymal stem cell secretome promotes hepatic regeneration in miniature pigs after liver ischaemia-reperfusion combined with partial resection

Jiao

Zhang

et al. 2021

Stem Cell Res Ther

View full text Add to dashboard Cite

Background Hepatic ischaemia-reperfusion injury (HIRI) is inevitable in complicated liver surgery and is a major factor leading to postoperative complications and liver dysfunction. Studies have shown that the paracrine mechanisms of stem cell may be essential to tissue repair and functional improvement after transplantation. However, the role of the adipose-derived mesenchymal stem cell secretome (ASC-secretome) in liver regeneration in large animals remains to be determined. Methods Twenty-four miniature pigs were subjected to laparoscopic liver ischaemia-reperfusion combined with partial hepatectomy and divided into the following four groups: the saline group, the DMEM group, the ASC group and the ASC-secretome group. Serum and liver tissue samples were collected before the operation and at 1, 3 and 7 days after the operation, and changes in tissue pathology, serum inflammation, liver function, angiogenesis-related factors and liver tissue regeneration-related genes and proteins were evaluated. Results Detailed histological analysis showed that ASCs and the ASC-secretome changed pathological damage to liver tissue after liver ischaemia-reperfusion combined with partial hepatectomy (1 and 3 days: p < 0.01). Compared with the saline and DMEM control groups, the ASC-secretome group had significantly reduced expression levels of ALP (1 and 3 days: p < 0.05), ALT (1 day: p < 0.01; 3 days: p < 0.05) and AST (1 and 3 days: p < 0.01), which promoted the recovery of liver function. Moreover, detection of the expression levels of TNF-α and IL-1β (1 day: p < 0.01; 3 days: p < 0.05), IL-6 (1 and 3 days: p < 0.05) and IL-10 (1 and 3 days: p < 0.01) in serum confirmed that the ASC-secretome had obvious anti-inflammatory effects. In addition, the ASC-secretome increased the expression levels of ANG-1 (3 days: p < 0.01), ANG-2 (3 and 7 days: p < 0.01) and VEGF (1 and 7 days: p < 0.05; 3 days: p < 0.01) and promoted angiogenesis during liver regeneration. Moreover, it promoted the mRNA expression of HGF and Cyclin D1 (1 and 3 days: p < 0.01); increased the levels of p-STAT3 (1 and 3 days: p < 0.01), PCNA and Ki67 (1 and 3 days: p < 0.01; 7 days: p < 0.05); inhibited the negative feedback of SOCS3 (1 and 3 days: p < 0.01); and decreased the mRNA expression of TGF-β (3 days: p < 0.01). The cytokines and growth factors detected in the ASC-secretome included TNF-α, IL-6, IL-1β, ANG-1, ANG-2, VEGF and b-FGF. Conclusion The ASC-secretome alleviates the inflammatory response induced by ischaemia-reperfusion combined with partial hepatectomy in miniature pigs and promotes liver regeneration.

show abstract

Mesenchymal stem cell-based cell-free strategies: safe and effective treatments for liver injury

Cited by 99 publications

References 102 publications

Molecular pathways of liver regeneration: A comprehensive review

Molecular pathways of liver regeneration: A comprehensive review

The Application of Mesenchymal Stem Cells in the Treatment of Liver Diseases: Mechanism, Efficacy, and Safety Issues

The adipose-derived mesenchymal stem cell secretome promotes hepatic regeneration in miniature pigs after liver ischaemia-reperfusion combined with partial resection

Contact Info

Product

Resources

About