Shortcut Route for Generation of Functional Hepatocyte Cells from Human Skin Allogenically for Autologous Treatment of Chronic Liver Diseases

Giri, Shibashish; Bader, Augustinus

doi:10.1016/j.jceh.2014.03.051

Cited by 2 publications

(2 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The liver requires healthy functional mitochondria to undertake the many functions attributed to this large organ, including metabolism of fats, proteins, and carbohydrates, storage of glycogen, and blood detoxification to name only a fraction [8]. The liver contains millions of hepatocytes, cells with a life span of ~150 days, and over half of the body’s supply of macrophages, known as Kupffer cells, needed to fight infections in the body [9,10]. Maintenance of a healthy level of these cells is another energy requiring function of the liver.…”

Section: Introductionmentioning

confidence: 99%

A Diet Induced Maladaptive Increase in Hepatic Mitochondrial DNA Precedes OXPHOS Defects and May Contribute to Non-Alcoholic Fatty Liver Disease

Malik

Simões

Rosa

et al. 2019

Cells

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD), an increasingly prevalent and underdiagnosed disease, is postulated to be caused by hepatic fat mediated pathological mechanisms. Mitochondrial dysfunction is proposed to be involved, but it is not known whether this is a pathological driver or a consequence of NAFLD. We postulate that changes to liver mitochondrial DNA (mtDNA) are an early event that precedes mitochondrial dysfunction and irreversible liver damage. To test this hypothesis, we evaluated the impact of diet on liver steatosis, hepatic mtDNA content, and levels of key mitochondrial proteins. Liver tissues from C57BL/6 mice fed with high fat (HF) diet (HFD) and Western diet (WD, high fat and high sugar) for 16 weeks were used. Steatosis/fibrosis were assessed using haematoxylin and eosin (H&E) Oil Red and Masson’s trichome staining and collagen content. Total DNA was isolated, and mtDNA content was determined by quantifying absolute mtDNA copy number/cell using quantitative PCR. Selected mitochondrial proteins were analysed from a proteomics screen. As expected, both HFD and WD resulted in steatosis. Mouse liver contained a high mtDNA content (3617 ± 233 copies per cell), which significantly increased in HFD diet, but this increase was not functional, as indicated by changes in mitochondrial proteins. In the WD fed mice, liver dysfunction was accelerated alongside downregulation of mitochondrial oxidative phosphorylation (OXPHOS) and mtDNA replication machinery as well as upregulation of mtDNA-induced inflammatory pathways. These results demonstrate that diet induced changes in liver mtDNA can occur in a relatively short time; whether these contribute directly or indirectly to subsequent mitochondrial dysfunction and the development of NAFLD remains to be determined. If this hypothesis can be substantiated, then strategies to prevent mtDNA damage in the liver may be needed to prevent development and progression of NAFLD.

show abstract

Section: Introductionmentioning

confidence: 99%

A Diet Induced Maladaptive Increase in Hepatic Mitochondrial DNA Precedes OXPHOS Defects and May Contribute to Non-Alcoholic Fatty Liver Disease

Malik

Simões

Rosa

et al. 2019

Cells

View full text Add to dashboard Cite

show abstract

“…Although previous studies reported that endothelial progenitor cells, mesenchymal stem cells and human amniotic epithelial cells could locate into the liver transiently after cell transplantation, our work firstly proved that dermal derived cells could efficiently implant in liver after intravenous transplantation. Furthermore, several previous studies reported hepatic-like cells could be induced from dermal cells 15 16 36 37 38 39 . However, we investigated the effects of dermal cells therapy for acute liver injury in vivo and found no hepatocytes differentiated from dermal cells in our present study.…”

Section: Disscussionmentioning

confidence: 99%

Contribution of dermal-derived mesenchymal cells during liver repair in two different experimental models

Tan

Dai

Liu

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Progressive liver disease is a major health issue for which no effective treatment is available, leading to cirrhosis and orthotopic liver transplantation. However, the lack of availability of donor organs and other adverse factors including rejection limit its extensive clinical application. Cell-based therapy using mesenchymal stem/stromal cells (MSCs) may represent an attractive therapeutic option. Dermal-derived mesenchymal cells (DMCs) are attractive as one of the abundant sources from which to isolate mesenchymal cells for therapeutic applications and can be easily accessed with minimal harm to the donor. In this study, we used two different animal models to investigate potential therapeutic effect of DMCs transplantation in liver injury. We found that DMCs administration alleviated liver fibrosis and restored the liver function in fibrotic mice induced by CCl4. Furthermore, in an acute irradiation induced damage model, a unique population of DMCs could engraft into the liver tissue for a long period, exhibiting the phenotype of both mesenchymal cells and macrophage cells, and improve the survival of mice exposed to 8 Gy lethally total-body irradiation. These discoveries provide important evidence that DMCs therapy has a beneficial effect on liver injury, and provide new insight into liver injury therapy depending on the alternative cells.

show abstract

Shortcut Route for Generation of Functional Hepatocyte Cells from Human Skin Allogenically for Autologous Treatment of Chronic Liver Diseases

Cited by 2 publications

References 16 publications

A Diet Induced Maladaptive Increase in Hepatic Mitochondrial DNA Precedes OXPHOS Defects and May Contribute to Non-Alcoholic Fatty Liver Disease

A Diet Induced Maladaptive Increase in Hepatic Mitochondrial DNA Precedes OXPHOS Defects and May Contribute to Non-Alcoholic Fatty Liver Disease

Contribution of dermal-derived mesenchymal cells during liver repair in two different experimental models

Contact Info

Product

Resources

About