Mesenchymal stem cells and Interleukin-6 attenuate liver fibrosis in mice

Journal of Translational Medicine

Sheikh Riazuddin¹  Shaheen N Khan¹  Gibran Ali¹  Sulaiman Shams¹  Mohsin Khan¹  Sadia Mohsin¹  Ghazanfar Ali Nasir¹ 

[1] National Center of Excellence in Molecular Biology, University of the Punjab, 87-West Canal Bank Road, Lahore, Pakistan

关键词: Interleukin-6;    Hepatocytes;    Liver fibrosis;    Mesenchymal stem cells;   

Others  :  827863
DOI  :  10.1186/1479-5876-11-78

 received in 2012-12-29, accepted in 2013-03-01,  发布年份 2013

【 摘 要 】

Background

Mesenchymal stem cell (MSC) transplantation has emerged as a promising therapy for liver fibrosis. Issues concerning poor MSC survival and engraftment in the fibrotic liver still persist and warrant development of a strategy to increase MSC potency for liver repair. The present study was designed to examine a synergistic role for Interleukin-6 (IL-6) and MSCs therapy in the recovery of carbon tetrachloride (CCl₄) induced injured hepatocytes in vitro and in vivo.

Methods

Injury was induced through 3 mM and 5 mM CCl₄ treatment of cultured hepatocytes while fibrotic mouse model was established by injecting 0.5 ml/kg CCl₄ followed by treatment with IL-6 and MSCs_. Effect of MSCs and IL-6 treatment on injured hepatocytes was determined by lactate dehydrogenase release, RT-PCR for (Bax, Bcl-xl, Caspase3, Cytokeratin 8, NFκB, TNF-α) and annexin V apoptotic detection. Analysis of MSC and IL-6 treatment on liver fibrosis was measured by histopathology, PAS, TUNEL and Sirius red staining, RT-PCR, and liver function tests for Bilirubin and Alkaline Phosphatase (ALP).

Results

A significant reduction in LDH release and apoptosis was observed in hepatocytes treated with a combination of MSCs and IL-6 concomitant with upregulation of anti-apoptotic gene Bcl-xl expression and down regulation of bax, caspase3, NFκB and TNF-α. Adoptive transfer of MSCs in fibrotic liver pretreated with IL-6 resulted increased MSCs homing and reduced fibrosis and apoptosis. Hepatic functional assessment demonstrated reduced serum levels of Bilirubin and ALP.

Conclusion

Pretreatment of fibrotic liver with IL-6 improves hepatic microenvironment and primes it for MSC transplantation leading to enhanced reduction of liver injury after fibrosis. Synergistic effect of IL-6 and MSCs seems a favored therapeutic option in attenuation of liver apoptosis and fibrosis accompanied by improved liver function.

【 授权许可】

   
2013 Nasir et al.; licensee BioMed Central Ltd.

【 图 表 】

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