Effect of bone marrow mesenchymal stem cell transplantation on acute hepatic failure in rats

Yuan,Shufang; Jiang,Tao; Zheng,Rongjiong; Sun,Lihua; Cao,Guiqiu; Zhang,Yuexin

doi:10.3892/etm.2014.1848

Effect of bone marrow mesenchymal stem cell transplantation on acute hepatic failure in rats

Authors:
- Shufang Yuan
- Tao Jiang
- Rongjiong Zheng
- Lihua Sun
- Guiqiu Cao
- Yuexin Zhang
View Affiliations

Affiliations: Department of Infectious Diseases, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China, Key Laboratory of Xinjiang Medical Animal Model Research, Urumqi, Xinjiang 830011, P.R. China, The Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China
Published online on: July 16, 2014 https://doi.org/10.3892/etm.2014.1848
Pages: 1150-1158

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to investigate the effectiveness of bone marrow mesenchymal stem cell (BMSC) transplantation in the treatment of acute hepatic failure (AHF) in rats. BMSCs were isolated from rat bone marrow, cultured and analyzed by flow cytometry. Following BMSC transplantation into rats with AHF, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), direct bilirubin (DBIL) and indirect bilirubin (IBIL) in the serum were measured using an automatic biochemical analyzer. Hematoxylin and eosin (H&E) staining and a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were performed to analyze the pathological changes and apoptosis rate. Levels of cluster of differentiation (CD)163 and interleukin (IL)‑10 in the serum and liver tissue were detected by an enzyme-linked immunosorbent assay (ELISA) assay and western blot analysis. Compared with the levels in the control group, the serum levels of ALT, AST, DBIL, IBIL, CD163 and IL‑10 in the BMSC transplantation groups were significantly lower at 120 and 168 h, while the serum levels of ALB were significantly higher at 168 h after BMSC transplantation. The pathological features of liver failure were alleviated by BMSC transplantation. The expression levels of CD163 and IL‑10 in the liver tissue were also significantly decreased following transplantation. The results indicate that BMSCs have a therapeutic effect on AHF in rats, and CD163 and IL‑10 may be used as sensitive serum prognosis indicators in the early assessment of patients following liver transplantation.

View Figures

View References

1	Lee WM, Squires RH Jr, Nyberg SL, Doo E and Hoofnagle JH: Acute liver failure: Summary of a workshop. Hepatology. 47:1401–1415. 2008.PubMed/NCBI
2	Kung JW and Forbes SJ: Stem cells and liver repair. Curr Opin Biotechnol. 20:568–574. 2009. View Article : Google Scholar
3	Oertel M and Shafritz DA: Stem cells, cell transplantation and liver repopulation. Biochim Biophys Acta. 1782:61–74. 2008. View Article : Google Scholar : PubMed/NCBI
4	Locke JE, Shamblott MJ and Cameron AM: Stem cells and the liver: clinical applications in transplantation. Adv Surg. 43:35–51. 2009. View Article : Google Scholar : PubMed/NCBI
5	Salama H, Zekri AR, Zern M, et al: Autologous hematopoietic stem cell transplantation in 48 patients with end-stage chronic liver diseases. Cell Transplant. 19:1475–1486. 2010. View Article : Google Scholar : PubMed/NCBI
6	Mark AL, Sun Z, Warren DS, et al: Stem cell mobilization is life saving in an animal model of acute liver failure. Ann Surg. 252:591–596. 2010.PubMed/NCBI
7	Antoniades CG, Berry PA, Wendon JA and Vergani D: The importance of immune dysfunction in determining outcome in acute liver failure. J Hepatol. 49:845–861. 2008. View Article : Google Scholar : PubMed/NCBI
8	Stuart WD, Kulkarni RM, Gray JK, Vasiliauskas J, Leonis MA and Waltz SE: Ron receptor regulates Kupffer cell-dependent cytokine production and hepatocyte survival following endotoxin exposure in mice. Hepatology. 53:1618–1628. 2011. View Article : Google Scholar : PubMed/NCBI
9	Taylor RC, Cullen SP and Martin SJ: Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol. 9:231–241. 2008. View Article : Google Scholar : PubMed/NCBI
10	Malhi H, Guicciardi ME and Gores GJ: Hepatocyte death: a clear and present danger. Physiol Rev. 90:1165–1194. 2010. View Article : Google Scholar : PubMed/NCBI
11	Sulahian TH, Hintz KA, Wardwell K and Guyre PM: Development of an ELISA to measure soluble CD163 in biological fluids. J Immunol Methods. 252:25–31. 2001. View Article : Google Scholar : PubMed/NCBI
12	Hiraoka A, Horiike N, Akbar SM, Michitaka K, Matsuyama T and Onji M: Soluble CD163 in patients with liver diseases: very high levels of soluble CD163 in patients with fulminant hepatic failure. J Gastroenterol. 40:52–56. 2005. View Article : Google Scholar : PubMed/NCBI
13	Sulahian TH, Högger P, Wahner AE, et al: Human monocytes express CD163, which is upregulated by IL-10 and identical to p155. Cytokine. 12:1312–1321. 2000. View Article : Google Scholar : PubMed/NCBI
14	Pae HO and Chung HT: Heme oxygenase-l: its therapeutic roles in inflammatory diseases. Immune Netw. 9:12–19. 2009. View Article : Google Scholar : PubMed/NCBI
15	Buechler C, Ritter M, Orsó E, Langmann T, Klucken J and Schmitz G: Regulation of scavenger receptor CD163 expression in human monocytes and macrophages by pro- and antiinflammatory stimuli. J Leukoc Biol. 67:97–103. 2000.PubMed/NCBI
16	Parekkadan B, van Poll D, Suganuma K, Carter EA, Berthiaume F, Tilles AW and Yarmush ML: Mesenchymal stem cell-derived molecules reverse fulminant hepatic failure. PLoS One. 2:e9412007. View Article : Google Scholar : PubMed/NCBI
17	Kuo TK, Hung SP, Chuang CH, et al: Stem cell therapy for liver disease: parameters governing the success of using bone marrow mesenchymal stem cells. Gastroenterology. 134:2111–2121. 2008. View Article : Google Scholar : PubMed/NCBI
18	Ismail A, Fouad O, Abdelnasser A, Chowdhury A and Selim A: Stem cell therapy improves the outcome of liver resection in cirrhotics. J Gastrointest Cancer. 41:17–23. 2010. View Article : Google Scholar : PubMed/NCBI
19	Stutchfield BM, Forbes SJ and Wigmore SJ: Prospects for stem cell transplantation in the treatment of hepatic disease. Liver Transpl. 16:827–836. 2010. View Article : Google Scholar : PubMed/NCBI
20	Cho KA, Ju SY, Cho SJ, et al: Mesenchymal stem cells showed the highest potential for the regeneration of injured liver tissue compared with other subpopulations of the bone marrow. Cell Biol Int. 33:772–777. 2009. View Article : Google Scholar : PubMed/NCBI
21	Enns GM and Millan MT: Cell-based therapies for metabolic liver disease. Mol Genet Metab. 95:3–10. 2008. View Article : Google Scholar
22	Miyazaki M, Hardjo M, Masaka T, et al: Isolation of a bone marrow-derived stem cell line with high proliferation potential and its application for preventing acute fatal liver failure. Stem Cells. 25:2855–2863. 2007. View Article : Google Scholar : PubMed/NCBI
23	Sensebé L and Bourin P: Mesenchymal stem cells for therapeutic purposes. Transplantation. 87(9 Suppl): S49–S53. 2009.
24	Miura M, Miura Y, Padilla-Nash HM, et al: Accumulated chromosomal instability in murine bone marrow mesenchymal stem cells leads to malignant transformation. Stem Cells. 24:1095–1103. 2006. View Article : Google Scholar : PubMed/NCBI
25	Liu F, Liu ZD, Wu N, Cong X, Fei R, Chen HS and Wei L: Transplanted endothelial progenitor cells ameliorate carbon tetrachloride-induced liver cirrhosis in rats. Liver Transpl. 15:1092–1100. 2009. View Article : Google Scholar : PubMed/NCBI
26	Muraca M: Evolving concepts in cell therapy of liver disease and current clinical perspectives. Dig Liver Dis. 43:180–187. 2011. View Article : Google Scholar : PubMed/NCBI
27	Rust C and Gores GJ: Apoptosis and liver disease. Am J Med. 108:567–574. 2000. View Article : Google Scholar
28	Ortiz LA, Dutreil M, Fattman C, Pandey AC, Torres G, Go K and Phinney DG: Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc Natl Acad Sci USA. 104:11002–11007. 2007. View Article : Google Scholar : PubMed/NCBI
29	Møller HJ, Frikke-Schmidt R, Moestrup SK, Nordestgaard BG and Tybjærg-Hansen A: Serum soluble CD163 predicts risk of type 2 diabetes in the general population. Clin Chem. 57:291–297. 2011.PubMed/NCBI
30	Louis H, Le Moine O, Peny MO, et al: Hepatoprotective role of interleukin 10 in galactosamine/lipopolysaccharide mouse liver injury. Gastroenterology. 112:935–942. 1997. View Article : Google Scholar : PubMed/NCBI
31	Philippidis P, Mason JC, Evans BJ, Nadra I, Taylor KM, Haskard DO and Landis RC: Hemoglobin scavenger receptor CDl63 mediates interleukin-10 release and heme oxygenase-1 synthesis: antiinflammatory monocyte-macrophage responses in vitro, in resolving skin blisters in vivo, and after cardiopulmonary bypass surgery. Circ Res. 94:119–126. 2004. View Article : Google Scholar
32	Fabriek BO, van Bruggen R, Deng DM, et al: The macrophage scavenger receptor CD163 functions as an innate immune sensor for bacteria. Blood. 113:887–892. 2009. View Article : Google Scholar : PubMed/NCBI
33	Moreno JA, Muñoz-García B, Martín-Ventura JL, et al: The CD163-expressing macrophages recognize and internalize TWEAK: potential consequences in atherosclerosis. Atherosclerosis. 207:103–110. 2009. View Article : Google Scholar : PubMed/NCBI