Transplantation of bone marrow–derived mesenchymal stem cells after regional hepatic irradiation ameliorates thioacetamide-induced liver fibrosis in rats

Shao, Chengchen; Chen, Shenglin; Dong, Tianfu; Chai, Hao; Yu, Yue; Deng, Lei; Wang, Yun; Cheng, Feng

doi:10.1016/j.jss.2013.08.016

Cited by 43 publications

(36 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Understanding the mechanism of IR injury is crucial to reducing liver injury during liver surgery. Pharmacological strategies, ischemic preconditioning or the application of new technologies have been shown to reduce liver IR injury (19,20). Our results, as well as those of a previous study have shown that ischemic preconditioning induces HO-1, alleviating IR liver injury (21).…”

Section: Discussionsupporting

confidence: 81%

ZnPP reduces autophagy and induces apoptosis, thus aggravating liver ischemia/reperfusion injury in vitro

Wang

Xiong

Guo

et al. 2014

International Journal of Molecular Medicine

Self Cite

View full text Add to dashboard Cite

Abstract. There is growing evidence indicating that autophagy plays a protective role in liver ischemia/reperfusion (IR) injury. Heme oxygenase-1 (HO-1) can also prevent liver IR injury by limiting inflammation and inducing an anti-apoptotic response. Autophagy also plays a crucial role in liver IR injury. The aim of the present study was to investigate the role of HO-1 in liver IR injury and the association between HO-1, autophagy and apoptotic pathways. IR simulation was performed using buffalo rat liver (BRL) cells, and HO-1 activity was either induced by hemin (HIR group) or inhibited by zinc protoporphyrin (ZnPP) (ZIR group). In the HIR and ZIR group, the expression of HO-1 and autophagy-related genes [light chain 3-Ⅱ (LC3-Ⅱ)] was assessed by RT-qPCR and the protein expression of caspases, autophagy-related genes and genes associated with apoptotic pathways (Bax) was detected by western blot anlaysis. The results of RT-PCR revealed the genetically decreased expression of HO-1 and autophagy-related genes in the ZIR group. Similar results were obtained by western blot analysis and immunofluorescence. An ultrastructural analysis revealed a lower number of autophagosomes in the ZIR group; in the HIR group, the number of autophagosomes was increased. The expression of Bax and cytosolic cytochrome c was increased, while that of Bcl-2 was decreased following treatment of the cells with ZnPP prior to IR simulation; the oppostie occurred in the HIR group. Cleaved caspase-3, caspase-9 and poly(ADPribose) polymerase (PARP) protein were activated in the IR and ZIR groups. The disruption of mitochondrial membrane potential was also observed in the ZIR group. In general, the downregulation of HO-1 reduced autophagy and activated the mitochondrial apoptotic pathway.

show abstract

Section: Discussionsupporting

confidence: 81%

ZnPP reduces autophagy and induces apoptosis, thus aggravating liver ischemia/reperfusion injury in vitro

Wang

Xiong

Guo

et al. 2014

International Journal of Molecular Medicine

Self Cite

View full text Add to dashboard Cite

show abstract

“…Heterotypic cell fusion was also observed in vivo between myeloid/lymphoid cells and non-haematopoietic cell lineages (including hepatocytes, cardiomyocytes and cerebellum Purkinje cells) after organspecific injuries or irradiation events, a feature found to be significantly enhanced in case of chronic inflammation [64]. Although no such mechanisms have been reported in vivo for MSCs they might be relevant when applied after regional hepatic irradiation in the context of liver fibrosis [65] (Fig. 2).…”

Section: Mscs Fusion and Exosome Release Propertiesmentioning

confidence: 95%

Mesenchymal Stem/Stromal Cells in Liver Fibrosis: Recent Findings, Old/New Caveats and Future Perspectives

Fiore

Mazzolini

Aquino

2015

Stem Cell Rev and Rep

View full text Add to dashboard Cite

Mesenchymal stem/stromal cells (MSCs) are progenitors which share plastic-adherence capacity and cell surface markers but have different properties according to their cell and tissue sources and to culture conditions applied. Many recent publications suggest that MSCs can differentiate into hepatic-like cells, which can be a consequence of either a positive selection of rare in vivo pluripotent cells or of the original plasticity of some cells contributing to MSC cultures. A possible role of MSCs in hereditary transmission of obesity and/or diabetes as well as properties of MSCs regarding immunomodulation, cell fusion and exosome release capacities are discussed according to recent literature. Limitations in methods used to track MSCs in vivo especially in the context of liver cirrhosis are addressed as well as strategies explored to enhance their migratory, survival and proliferation properties, which are known to be relevant for their future clinical use. Current knowledge regarding mechanisms involved in liver cirrhosis amelioration mediated by naïve and genetically modified MSCs as well as the effects of applying preconditioning and combined strategies to improve their therapeutic effects are evaluated. Finally, first reports of GMP guidelines and biosafety issues in MSCs applications are discussed.

show abstract

“…However, the exact mechanisms have been subject to some controversy: In one mouse model, no measurable numbers of MSCs could be detected in the irradiated liver tissue, and the beneficial effects of MSC-based treatment of liver damage were attributed to the cells' paracrine and immunomodulatory functions [49,51]. Other studies reported increased homing and engraftment of MSCs into damaged liver tissue up to 3 weeks after high-dose liver irradiation as well as cellular cytokeratin 18/19 and AFP expression, suggesting an involvement of the cells' migratory and differentiation capabilities in the attenuation of radiationinduced liver damage [50,52]. On a molecular level, MSCs at sites of liver damage were found to secrete neural and hepatocyte growth factors and anti-inflammatory molecules IL-10 and IL1RA, thereby reducing apoptosis levels and increased hepatocyte proliferation [50].…”

Section: Livermentioning

confidence: 99%

Mesenchymal stem cells – A new hope for radiotherapy-induced tissue damage?

et al. 2015

View full text Add to dashboard Cite

Transplantation of bone marrow–derived mesenchymal stem cells after regional hepatic irradiation ameliorates thioacetamide-induced liver fibrosis in rats

Cited by 43 publications

References 51 publications

ZnPP reduces autophagy and induces apoptosis, thus aggravating liver ischemia/reperfusion injury in vitro

ZnPP reduces autophagy and induces apoptosis, thus aggravating liver ischemia/reperfusion injury in vitro

Mesenchymal Stem/Stromal Cells in Liver Fibrosis: Recent Findings, Old/New Caveats and Future Perspectives

Mesenchymal stem cells – A new hope for radiotherapy-induced tissue damage?

Contact Info

Product

Resources

About