Serum from hepatectomized rats induces the differentiation of adipose tissue mesenchymal stem cells into hepatocyte-like cells and upregulates the expression of hepatocyte growth factor and interleukin-6 in vitro

Sun,Jiangyang; Yuan,Yufeng; Qin,Haiquan; Ying,Chengcheng; Liu,Weijun; Zhang,Jin; He,Yueming; Liu,Zhisu

doi:10.3892/ijmm.2013.1257

Serum from hepatectomized rats induces the differentiation of adipose tissue mesenchymal stem cells into hepatocyte-like cells and upregulates the expression of hepatocyte growth factor and interleukin-6 in vitro

Authors:
- Jiangyang Sun
- Yufeng Yuan
- Haiquan Qin
- Chengcheng Ying
- Weijun Liu
- Jin Zhang
- Yueming He
- Zhisu Liu
View Affiliations

Affiliations: Department of General Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China, Department of Urology Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
Published online on: January 23, 2013 https://doi.org/10.3892/ijmm.2013.1257
Pages: 667-675

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

Adipose tissue-derived mesenchymal stem cells (AT-MSCs) are an attractive alternative for clinical application due to their minimally invasive accessibility and availability in the body. However, the hepatic differentiation efficiency of AT-MSCs is insufﬁcient for therapeutic application and the role of extrahepatic stem cells in liver regeneration remains poorly understood. This study was designed to investigate the effects of serum from rats subjected to 70% partial hepatectomy (PH) on the differentiation ability of rat AT-MSCs in vitro, and to explore the potential role of AT-MSCs in vivo following PH injury. Results showed that AT-MSCs treated with serum collected from rats 24 h after 70% PH differentiated into hepatocyte-like cells, resembled hepatocyte-like cells with round or polygonal shape, expressed α-fetoprotein, secreted albumin, synthesized urea and acquired cytochrome P450 type 3A4 enzyme activity, and upregulated the expression of interleukin (IL)-6 and hepatocyte growth factor (HGF) transiently in vitro, although the hepatic differentiation efficiency was extremely low. AT-MSC transplantation after 70% PH ameliorated liver injury and promoted liver regeneration, but did not increase the serum levels of IL-6 and HGF in vivo. This result suggests that the therapeutic effect of AT-MSCs in vivo after 24 h of 70% PH does not increase IL-6 and HGF expression.

View Figures

View References

1	Banas A, Teratani T, Yamamoto Y, et al: Rapid hepatic fate specification of adipose-derived stem cells and their therapeutic potential for liver failure. J Gastroenterol Hepatol. 24:70–77. 2009. View Article : Google Scholar : PubMed/NCBI
2	Banas A, Teratani T, Yamamoto Y, et al: Adipose tissue-derived mesenchymal stem cells as a source of human hepatocytes. Hepatology. 46:219–228. 2007.PubMed/NCBI
3	Sgodda M, Aurich H, Kleist S, et al: Hepatocyte differentiation of mesenchymal stem cells from rat peritoneal adipose tissue in vitro and in vivo. Exp Cell Res. 313:2875–2886. 2007. View Article : Google Scholar : PubMed/NCBI
4	Yamamoto Y, Banas A, Murata S, et al: A comparative analysis of the transcriptome and signal pathways in hepatic differentiation of human adipose mesenchymal stem cells. FEBS J. 275:1260–1273. 2008. View Article : Google Scholar : PubMed/NCBI
5	Talens-Visconti R, Bonora A, Jover R, et al: Hepatogenic differentiation of human mesenchymal stem cells from adipose tissue in comparison with bone marrow mesenchymal stem cells. World J Gastroenterol. 12:5834–5845. 2006.PubMed/NCBI
6	Snykers S, Vanhaecke T, Papeleu P, et al: Sequential exposure to cytokines reflecting embryogenesis: the key for in vitro differentiation of adult bone marrow stem cells into functional hepatocyte-like cells. Toxicol Sci. 94:330–341. 2006. View Article : Google Scholar : PubMed/NCBI
7	Michalopoulos GK: Liver regeneration. J Cell Physiol. 213:286–300. 2007. View Article : Google Scholar : PubMed/NCBI
8	Taub R: Liver regeneration: from myth to mechanism. Nat Rev Mol Cell Biol. 5:836–847. 2004. View Article : Google Scholar : PubMed/NCBI
9	Brand S, Beigel F, Olszak T, et al: IL-22 is increased in active Crohn’s disease and promotes proinflammatory gene expression and intestinal epithelial cell migration. Am J Physiol Gastrointest Liver Physiol. 290:G827–G838. 2006.
10	Cressman DE, Greenbaum LE, DeAngelis RA, et al: Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice. Science. 274:1379–1383. 1996. View Article : Google Scholar : PubMed/NCBI
11	Ren X, Hogaboam C, Carpenter A and Colletti L: Stem cell factor restores hepatocyte proliferation in IL-6 knockout mice following 70% hepatectomy. J Clin Invest. 112:1407–1418. 2003.PubMed/NCBI
12	Moolten FL and Bucher NL: Regeneration of rat liver: transfer of humoral agent by cross circulation. Science. 158:272–274. 1967. View Article : Google Scholar : PubMed/NCBI
13	Jirtle RL and Michalopoulos G: Effects of partial hepatectomy on transplanted hepatocytes. Cancer Res. 42:3000–3004. 1982.PubMed/NCBI
14	Wang PP, Wang JH, Yan ZP, et al: Expression of hepatocyte-like phenotypes in bone marrow stromal cells after HGF induction. Biochem Biophys Res Commun. 320:712–716. 2004. View Article : Google Scholar : PubMed/NCBI
15	Yang Y, Qu B, Huo JH, Wu SL, Zhang MY and Wang ZR: Serum from radiofrequency-injured livers induces differentiation of bone marrow stem cells into hepatocyte-like cells. J Surg Res. 155:18–24. 2009. View Article : Google Scholar : PubMed/NCBI
16	Seo MJ, Suh SY, Bae YC and Jung JS: Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo. Biochem Biophys Res Commun. 328:258–264. 2005. View Article : Google Scholar : PubMed/NCBI
17	Greene AK and Puder M: Partial hepatectomy in the mouse: technique and perioperative management. J Invest Surg. 16:99–102. 2003. View Article : Google Scholar : PubMed/NCBI
18	Hatch HM, Zheng D, Jorgensen ML and Petersen BE: SDF-1alpha/CXCR4: a mechanism for hepatic oval cell activation and bone marrow stem cell recruitment to the injured liver of rats. Cloning Stem Cells. 4:339–351. 2002. View Article : Google Scholar : PubMed/NCBI
19	Dalakas E, Newsome PN, Harrison DJ and Plevris JN: Hematopoietic stem cell trafficking in liver injury. FASEB J. 19:1225–1231. 2005. View Article : Google Scholar : PubMed/NCBI
20	Gomez-Aristizabal A, Keating A and Davies JE: Mesenchymal stromal cells as supportive cells for hepatocytes. Mol Ther. 17:1504–1508. 2009. View Article : Google Scholar : PubMed/NCBI
21	Schafer M and Werner S: Transcriptional control of wound repair. Annu Rev Cell Dev Biol. 23:69–92. 2007. View Article : Google Scholar
22	Mitchell C and Fausto N: Bone marrow-derived hepatocytes: rare but promising. Am J Pathol. 161:349–350. 2002. View Article : Google Scholar : PubMed/NCBI
23	Fausto N: Liver regeneration and repair: hepatocytes, progenitor cells, and stem cells. Hepatology. 39:1477–1487. 2004. View Article : Google Scholar : PubMed/NCBI
24	Malhi H and Gupta S: Hepatocyte transplantation: new horizons and challenges. J Hepatobiliary Pancreat Surg. 8:40–50. 2001. View Article : Google Scholar : PubMed/NCBI
25	Menthena A, Deb N, Oertel M, et al: Bone marrow progenitors are not the source of expanding oval cells in injured liver. Stem Cells. 22:1049–1061. 2004.PubMed/NCBI
26	Wang J, Clark JB, Rhee GS, Fair JH, Reid LM and Gerber DA: Proliferation and hepatic differentiation of adult-derived progenitor cells. Cells Tissues Organs. 173:193–203. 2003. View Article : Google Scholar : PubMed/NCBI
27	Caplan AI and Dennis JE: Mesenchymal stem cells as trophic mediators. J Cell Biochem. 98:1076–1084. 2006. View Article : Google Scholar : PubMed/NCBI
28	Parekkadan B, van Poll D, Suganuma K, et al: Mesenchymal stem cell-derived molecules reverse fulminant hepatic failure. PLoS One. 2:e9412007. View Article : Google Scholar : PubMed/NCBI
29	Parekkadan B, van Poll D, Megeed Z, et al: Immunomodulation of activated hepatic stellate cells by mesenchymal stem cells. Biochem Biophys Res Commun. 363:247–252. 2007. View Article : Google Scholar : PubMed/NCBI
30	Sadat S, Gehmert S, Song YH, et al: The cardioprotective effect of mesenchymal stem cells is mediated by IGF-I and VEGF. Biochem Biophys Res Commun. 363:674–679. 2007. View Article : Google Scholar : PubMed/NCBI
31	Gnecchi M, He H, Noiseux N, et al: Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. FASEB J. 20:661–669. 2006. View Article : Google Scholar
32	Shito M, Balis UJ, Tompkins RG, Yarmush ML and Toner M: A fulminant hepatic failure model in the rat: involvement of interleukin-1beta and tumor necrosis factor-alpha. Dig Dis Sci. 46:1700–1708. 2001. View Article : Google Scholar : PubMed/NCBI
33	Gnecchi M, Zhang Z, Ni A and Dzau VJ: Paracrine mechanisms in adult stem cell signaling and therapy. Circ Res. 103:1204–1219. 2008. View Article : Google Scholar : PubMed/NCBI
34	van Poll D, Parekkadan B, Cho CH, et al: Mesenchymal stem cell-derived molecules directly modulate hepatocellular death and regeneration in vitro and in vivo. Hepatology. 47:1634–1643. 2008.PubMed/NCBI
35	Banas A, Teratani T, Yamamoto Y, et al: IFATS collection: in vivo therapeutic potential of human adipose tissue mesenchymal stem cells after transplantation into mice with liver injury. Stem Cells. 26:2705–2712. 2008. View Article : Google Scholar
36	Miyazaki M, Akiyama I, Sakaguchi M, et al: Improved conditions to induce hepatocytes from rat bone marrow cells in culture. Biochem Biophys Res Commun. 298:24–30. 2002. View Article : Google Scholar : PubMed/NCBI
37	Wen Q, Zhou L, Zhou C, Zhou M, Luo W and Ma L: Change in hepatocyte growth factor concentration promote mesenchymal stem cell-mediated osteogenic regeneration. J Cell Mol Med. 16:1260–1273. 2012. View Article : Google Scholar : PubMed/NCBI
38	Pricola KL, Kuhn NZ, Haleem-Smith H, Song Y and Tuan RS: Interleukin-6 maintains bone marrow-derived mesenchymal stem cell stemness by an ERK1/2-dependent mechanism. J Cell Biochem. 108:577–588. 2009. View Article : Google Scholar : PubMed/NCBI
39	Lam SP, Luk JM, Man K, et al: Activation of interleukin-6-induced glycoprotein 130/signal transducer and activator of transcription 3 pathway in mesenchymal stem cells enhances hepatic differentiation, proliferation, and liver regeneration. Liver Transpl. 16:1195–1206. 2010. View Article : Google Scholar
40	Shiota G and Kawasaki H: Hepatocyte growth factor in transgenic mice. Int J Exp Pathol. 79:267–277. 1998. View Article : Google Scholar : PubMed/NCBI
41	Ueki T, Kaneda Y, Tsutsui H, et al: Hepatocyte growth factor gene therapy of liver cirrhosis in rats. Nat Med. 5:226–230. 1999. View Article : Google Scholar : PubMed/NCBI
42	Yu Y, Lu L, Qian X, et al: Antifibrotic effect of hepatocyte growth factor-expressing mesenchymal stem cells in small-for-size liver transplant rats. Stem Cells Dev. 19:903–914. 2010. View Article : Google Scholar : PubMed/NCBI
43	Kumamaru H, Ohkawa Y, Saiwai H, et al: Direct isolation and RNA-seq reveal environment-dependent properties of engrafted neural stem/progenitor cells. Nat Commun. 3:11402012. View Article : Google Scholar : PubMed/NCBI