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BY-NC-ND 3.0 license Open Access Published by De Gruyter April 24, 2012

Maintenance of rat hepatocytes under inflammation by coculture with human orbital fat-derived stem cells

  • Xia Chen EMAIL logo , Shichang Zhang , Tao Liu , Yong Liu and Yingjie Wang

Abstract

Preservation of hepatocyte functions in vitro will undoubtedly help the management of acute liver failure. The coculture system may be able to prevent functional decline of hepatocytes. It has already been shown that hepatocytes, when cocultured with bone marrow mesenchymal stem cells, could undergo long-term culture in vitro without loss of functions. In this study, human orbital fat-derived stem cells were isolated and cocultured with rat hepatocytes. When treated with serum from an acute liver failure patient, rat hepatocyte monoculture showed reduction of cell viability and loss of liverspecific functions. However, rat hepatocytes in the coculture system were still able to secret albumin and synthesize urea. IL-6 was significantly elevated in the coculture of rat hepatocyte with orbital fat-derived stem cells, and it might be the key immunoregulator which protects rat hepatocytes against inflammation. Our data confirmed that orbital fat-derived stem cells, or other adipose tissue-derived stem cells, are an ideal candidate to support rat hepatocyte functions in vitro.

[1] Bernal, W., Auzinger, G., Dhawan, A. and Wendon, J. Acute liver failure. Lancet 376 (2010) 190–201. http://dx.doi.org/10.1016/S0140-6736(10)60274-710.1016/S0140-6736(10)60274-7Search in Google Scholar

[2] Dhawan, A., Puppi, J., Hughes, R.D. and Mitry, R.R. Human hepatocyte transplantation: current experience and future challenges. Nat. Rev. Gastroenterol. Hepatol. 7 (2010) 288–298. http://dx.doi.org/10.1038/nrgastro.2010.4410.1038/nrgastro.2010.44Search in Google Scholar

[3] Phua, J. and Lee, K.H. Liver support devices. Curr. Opin. Crit. Care 14 (2008) 208–215. http://dx.doi.org/10.1097/MCC.0b013e3282f7005710.1097/MCC.0b013e3282f70057Search in Google Scholar

[4] Elaut, G., Henkens, T., Papeleu, P., Snykers, S., Vinken, M., Vanhaecke, T. and Rogiers, V. Molecular mechanisms underlying the dedifferentiation process of isolated hepatocytes and their cultures. Curr. Drug Metab. 7 (2006) 629–660. http://dx.doi.org/10.2174/13892000677801775910.2174/138920006778017759Search in Google Scholar

[5] Kaihara, S., Kim, S., Kim, B.S., Mooney, D.J., Tanaka, K. and Vacanti, J.P. Survival and function of rat hepatocytes cocultured with nonparenchymal cells or sinusoidal endothelial cells on biodegradable polymers under flow conditions. J. Pediatr. Surg. 35 (2000) 1287–1290. http://dx.doi.org/10.1053/jpsu.2000.929810.1053/jpsu.2000.9298Search in Google Scholar

[6] Mizuguchi, T., Palm, K., Hui, T., Aoki, T., Mochizuki, Y., Mitaka, T., Demetriou, A.A. and Rozga, J. Effects of bone marrow stromal cells on the structural and functional polarity of primary rat hepatocytes. In Vitro Cell Dev. Biol. Anim. 38 (2002) 62–65. http://dx.doi.org/10.1290/1071-2690(2002)038<0062:EOBMSC>2.0.CO;210.1290/1071-2690(2002)038<0062:EOBMSC>2.0.CO;2Search in Google Scholar

[7] Isoda, K., Kojima, M., Takeda, M., Higashiyama, S., Kawase, M. and Yagi, K. Maintenance of hepatocyte functions by coculture with bone marrow stromal cells. J. Biosci. Bioeng. 97 (2004) 343–346. Search in Google Scholar

[8] Ijima, H., Murakami, S., Matsuo, T., Takei, T., Ono, T. and Kawakami, K. Enhancement of liver-specific functions of primary rat hepatocytes cocultured with bone marrow cells on tissue culture-treated polystyrene surfaces. J. Artif. Organs 8 (2005) 104–109. http://dx.doi.org/10.1007/s10047-005-0289-910.1007/s10047-005-0289-9Search in Google Scholar

[9] Gu, J., Shi, X., Chu, X., Zhang, Y. and Ding, Y. Contribution of bone marrow mesenchymal stem cells to porcine hepatocyte culture in vitro. Biochem. Cell Biol. 87 (2009) 595–604. http://dx.doi.org/10.1139/O09-01710.1139/O09-017Search in Google Scholar

[10] Takeda, M., Yamamoto, M., Isoda, K., Higashiyama, S., Hirose, M., Ohgushi, H., Kawase, M. and Yagi, K. Availability of bone marrow stromal cells in three-dimensional coculture with hepatocytes and transplantation into liver-damaged mice. J. Biosci. Bioeng. 100 (2005) 77–81. http://dx.doi.org/10.1263/jbb.100.7710.1263/jbb.100.77Search in Google Scholar

[11] Yagi, H., Parekkadan, B., Suganuma, K., Soto-Gutierrez, A., Tompkins, R.G., Tilles, A.W. and Yarmush, M.L. Long-term superior performance of a stem cell/hepatocyte device for the treatment of acute liver failure. Tissue Eng. Part A 15 (2009) 3377–3388. http://dx.doi.org/10.1089/ten.tea.2008.068110.1089/ten.tea.2008.0681Search in Google Scholar

[12] Zuk, P.A., Zhu, M., Mizuno, H., Huang, J., Futrell, J.W., Katz, A.J., Benhaim, P., Lorenz, H.P. and Hedrick, M.H. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 7 (2001) 211–228. http://dx.doi.org/10.1089/10763270130006285910.1089/107632701300062859Search in Google Scholar PubMed

[13] Ho, J.H., Ma, W.H., Tseng, T.C., Chen, Y.F., Chen, M.H. and Lee, O.K. Isolation and characterization of multi-potent stem cells from human orbital fat tissues. Tissue Eng. Part A 17 (2011) 255–266. http://dx.doi.org/10.1089/ten.tea.2010.010610.1089/ten.tea.2010.0106Search in Google Scholar

[14] Tanaka, K., Soto-Gutierrez, A., Navarro-Alvarez, N., Rivas-Carrillo, J.D., Jun, H.S. and Kobayashi, N. Functional hepatocyte culture and its application to cell therapies. Cell Transplant. 15 (2006) 855–864. http://dx.doi.org/10.3727/00000000678398133210.3727/000000006783981332Search in Google Scholar PubMed

[15] Wu, Z., Han, M., Chen, T., Yan, W. and Ning, Q. Acute liver failure: mechanisms of immune-mediated liver injury. Liver Int. 30 (2010) 782–794. http://dx.doi.org/10.1111/j.1478-3231.2010.02262.x10.1111/j.1478-3231.2010.02262.xSearch in Google Scholar PubMed

[16] Ishikawa, T., Banas, A., Hagiwara, K., Iwaguro, H. and Ochiya, T. Stem cells for hepatic regeneration: the role of adipose tissue derived mesenchymal stem cells. Curr. Stem Cell Res. Ther. 5 (2010) 182–189. http://dx.doi.org/10.2174/15748881079126863610.2174/157488810791268636Search in Google Scholar PubMed

[17] Yanez, R., Lamana, M.L., Garcia-Castro, J., Colmenero, I., Ramirez, M. and Bueren, J.A. Adipose tissue-derived mesenchymal stem cells have in vivo immunosuppressive properties applicable for the control of the graft-versushost disease. Stem Cells 24 (2006) 2582–2591. http://dx.doi.org/10.1634/stemcells.2006-022810.1634/stemcells.2006-0228Search in Google Scholar PubMed

[18] Gonzalez, M.A., Gonzalez-Rey, E., Rico, L., Buscher, D. and Delgado, M. Treatment of experimental arthritis by inducing immune tolerance with human adipose-derived mesenchymal stem cells. Arthritis Rheum. 60 (2009) 1006–1019. http://dx.doi.org/10.1002/art.2440510.1002/art.24405Search in Google Scholar PubMed

[19] Salgado, A.J., Reis, R.L., Sousa, N.J. and Gimble, J.M. Adipose tissue derived stem cells secretome: soluble factors and their roles in regenerative medicine. Curr. Stem Cell Res. Ther. 5 (2010) 103–110. http://dx.doi.org/10.2174/15748881079126856410.2174/157488810791268564Search in Google Scholar PubMed

[20] Horras, C.J., Lamb, C.L. and Mitchell, K.A. Regulation of hepatocyte fate by interferon-gamma. Cytokine Growth Factor Rev. 22 (2011) 35–43. http://dx.doi.org/10.1016/j.cytogfr.2011.01.00110.1016/j.cytogfr.2011.01.001Search in Google Scholar PubMed PubMed Central

[21] Mao, R, Zhang, J., Jiang, D., Cai, D., Levy, J.M., Cuconati, A., Block, T.M., Guo, J.T. and Guo, H. Indoleamine 2,3-dioxygenase mediates the antiviral effect of gamma interferon against hepatitis B virus in human hepatocyte-derived cells. J. Virol. 85 (2011) 1048–1057. http://dx.doi.org/10.1128/JVI.01998-1010.1128/JVI.01998-10Search in Google Scholar PubMed PubMed Central

[22] Yuceturk, H., Yagmurdur, M.C., Gur, G., Demirbilek, M., Bilezikci, B., Turan, M., Karakayali, H. and Haberal, M. Role of heparin on TNF-α and IL-6 levels in liver regeneration after partial hepatic resection. Eur. Surg. Res. 39 (2007) 216–221. http://dx.doi.org/10.1159/00010174410.1159/000101744Search in Google Scholar PubMed

[23] Lin, Y.C., Goto, S., Tateno, C., Nakano, T., Cheng, Y.F., Jawan, B., Kao, Y.H., Hsu, L.W., Lai, C.Y., Yoshizato, K. and Chen, C.L. Induction of indoleamine 2,3-dioxygenase in livers following hepatectomy prolongs survival of allogeneic hepatocytes after transplantation. Transplant. Proc. 40 (2008) 2706–2708. http://dx.doi.org/10.1016/j.transproceed.2008.08.00110.1016/j.transproceed.2008.08.001Search in Google Scholar PubMed

[24] Kishimoto, T. IL-6: from its discovery to clinical applications. Int. Immunol. 22 (2010) 347–352. http://dx.doi.org/10.1093/intimm/dxq03010.1093/intimm/dxq030Search in Google Scholar PubMed

[25] Tiberio, L., Tiberio, G.A., Bardella, L., Cervi, E., Cerea, K., Dreano, M., Garotta, G., Fra, A., Montani, N., Ferrari-Bravo, A., Callea, F., Grigolato, P., Giulini, S.M. and Schiaffonati, L. Mechanisms of interleukin-6 protection against ischemia-reperfusion injury in rat liver. Cytokine 34 (2006) 131–142. http://dx.doi.org/10.1016/j.cyto.2006.04.00910.1016/j.cyto.2006.04.009Search in Google Scholar PubMed

[26] Banas, A., Teratani, T., Yamamoto, Y., Tokuhara, M., Takeshita, F., Quinn, G., Okochi, H. and Ochiya, T. Adipose tissue-derived mesenchymal stem cells as a source of human hepatocytes. Hepatology 46 (2007) 219–228. http://dx.doi.org/10.1002/hep.2170410.1002/hep.21704Search in Google Scholar PubMed

[27] Talens-Visconti, R., Bonora, A., Jover, R., Mirabet, V., Carbonell, F., Castell, J.V. and Gómez-Lechón, M.J. Hepatogenic differentiation of human mesenchymal stem cells from adipose tissue in comparison with bone marrow mesenchymal stem cells. World J. Gastroenterol. 12 (2006) 5834–5845. Search in Google Scholar

[28] Banas, A., Teratani, T., Yamamoto, Y., Tokuhara, M., Takeshita, F., Osaki, M., Kato, T., Okochi, H. and Ochiya, T. Rapid hepatic fate specification of adipose-derived stem cells and their therapeutic potential for liver failure. J. Gastroenterol. Hepatol. 24 (2009) 70–77. http://dx.doi.org/10.1111/j.1440-1746.2008.05496.x10.1111/j.1440-1746.2008.05496.xSearch in Google Scholar PubMed

[29] Banas, A., Teratani, T., Yamamoto, Y., Tokuhara, M., Takeshita, F., Osaki, M., Kawamata, M., Kato, T., Okochi, H. and Ochiya, T. IFATS collection: in vivo therapeutic potential of human adipose tissue mesenchymal stem cells after transplantation into mice with liver injury. Stem Cells 26 (2008) 2705–2712. http://dx.doi.org/10.1634/stemcells.2008-003410.1634/stemcells.2008-0034Search in Google Scholar PubMed

Published Online: 2012-4-24
Published in Print: 2012-6-1

© 2012 University of Wrocław, Poland

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

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