JRM Vol.25 No.4 pp. 698-704
doi: 10.20965/jrm.2013.p0698


Control of Liver Tissue Reconstitution in Mesenteric Leaves: The Effect of Preculture on Mouse Hepatic Progenitor Cells Prior to Transplantation

Nobuhiko Kojima and Yasuyuki Sakai

Institute of Industrial Science (IIS), The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan

January 29, 2013
May 21, 2013
August 20, 2013
liver tissue engineering, extrahepatic implantation, hepatic progenitor cell, mesenteric transplantation, highly porous biodegradable scaffold
Our objective is to control the reconstitution of liverlike tissues at extrahepatic sites using hepatic progenitor cells (HPCs) and in vitro preculture prior to transplantation. We prepared cell-based hybrid grafts by culturing HPCs isolated from fetal E14.5 mouse livers on biodegradable, highly porous 3-dimensional poly-L-lactic acid (PLLA) scaffolds for 1 week in basal medium (the basal condition) or 10 mM nicotinamide (NA) and 1% dimethyl sulfoxide (DMSO) supplemented conditions (the ND-positive condition) prior to implantation. Sections of hybrid grafts cultured for 1 week showed that HPCs grew and spread on the surface of scaffolds under both basal and ND (+) conditions. Most of these cells were albumin (+) and CK18 (+). CK19 (+) cells were also present under the basal condition but not the ND (+) condition. Cultured hybrid grafts were implanted into the mesenteric leaves of mice and removed after 1 month. Transplanted tissues cultured under the basal condition consisted of albumin (+) hepatocyte-like and CK19 (+) biliary epithelial cell (BEC)-like cells organized in duct-like structures. In contrast, integrated tissues cultured under the ND (+) condition alone had differentiated albumin (+) hepatocyte-like cells and were relatively larger than those under the basal condition. Hepatocyte-like cells of transplanted hybrid grafts cultured under both conditions were periodic acid-Schiff (PAS) staining-positive and expressed transcription factors, hepatocyte nuclear factor (HNF) 4 and CCAAT/enhancer-binding protein (C/EBP) α. These findings suggest that combining progenitor cells and in vitro preculture may potentially regulate liverlike tissues at extrahepatic sites.
Cite this article as:
N. Kojima and Y. Sakai, “Control of Liver Tissue Reconstitution in Mesenteric Leaves: The Effect of Preculture on Mouse Hepatic Progenitor Cells Prior to Transplantation,” J. Robot. Mechatron., Vol.25 No.4, pp. 698-704, 2013.
Data files:
  1. [1] A. M. Cameron, R. M. Ghobrial, H. Yersiz, D. G. Farmer, G. S. Lipshutz, S. A. Gordon, M. Zimmerman, J. Hong, T. E. Collins, J. Gornbein, F. Amersi, M. Weaver, C. Cao, T. Chen, J. R. Hiatt, and R. W. Busuttil, “Optimal utilization of donor grafts with extended criteria: a single-center experience in over 1000 liver transplants,” Ann. Surg., Vol.243, No.6, pp. 748-753, discussion 753-745, 2006.
  2. [2] T. Katsuda, T. Teratani, T. Ochiya, and Y. Sakai, “Transplantation of a fetal liver cell-loaded hyaluronic acid sponge onto the mesentery recovers a Wilson’s disease model rat,” “J. Biochem., Vol.148, No.3, pp. 281-288, 2010.
  3. [3] S. Uyama, P. M. Kaufmann, T. Takeda, and J. P. Vacanti, “Delivery of whole liver-equivalent hepatocyte mass using polymer devices and hepatotrophic stimulation,” Transplantation, Vol.55, No.4, pp. 932-935, 1993.
  4. [4] J. P. Vacanti, M. A. Morse, W. M. Saltzman, A. J. Domb, A. Perez-Atayde, and R. Langer, “Selective cell transplantation using bioabsorbable artificial polymers as matrices,” J. Pediatr. Surg., Vol.23, No.1, Pt.2, pp. 3-9, 1988.
  5. [5] K. Ohashi, K. Tatsumi, R. Utoh, S. Takagi,M. Shima, and T. Okano, “Engineering liver tissues under the kidney capsule site provides therapeutic effects to hemophilia B mice,” Cell Transplant, Vol.19, No.6, pp. 807-813, 2010.
  6. [6] K. Ohashi, J. M. Waugh, M. D. Dake, T. Yokoyama, H. Kuge, Y. Nakajima, M. Yamanouchi, H. Naka, A. Yoshioka, and M. A. Kay, “Liver tissue engineering at extrahepatic sites in mice as a potential new therapy for genetic liver diseases,” Hepatology, Vol.41, No.1, pp. 132-140, 2005.
  7. [7] C. Ricordi, P. E. Lacy, M. P. Callery, P. W. Park, and M. W. Flye, “Trophic factors from pancreatic islets in combined hepatocyte-islet allografts enhance hepatocellular survival,” Surgery, Vol.105, No.2, Pt.1, pp. 218-223, 1989.
  8. [8] M. Kusano and M. Mito, “Observations on the fine structure of long-survived isolated hepatocytes inoculated into rat spleen,” Gastroenterology, Vol.82, No.4, pp. 616-628, 1982.
  9. [9] M. Mito, H. Ebata, M. Kusano, T. Onishi, T. Saito, and S. Sakamoto, “Morphology and function of isolated hepatocytes transplanted into rat spleen,” Transplantation, Vol.28, No.6, pp. 499-505, 1979.
  10. [10] S. C. Strom, R. A. Fisher, M. T. Thompson, A. J. Sanyal, P. E. Cole, J. M. Ham, and M. P. Posner, “Hepatocyte transplantation as a bridge to orthotopic liver transplantation in terminal liver failure,” Transplantation, Vol.63, No.4, pp. 559-569, 1997.
  11. [11] T. Yamamoto, N. Navarro-Alvarez, A. Soto-Gutierrez, T. Yuasa, M. Iwamuro, Y. Kubota, M. Seita, H. Kawamoto, S. M. Javed, E. Kondo, H. Noguchi, S. Kobayashi, S. Nakaji, and N. Kobayashi, “Treatment of acute liver failure in mice by hepatocyte xenotransplantation,” Cell Transplant, Vol.19, No.6, pp. 799-806, 2010.
  12. [12] A. A. Demetriou, S. M. Levenson, P. M. Novikoff, A. B. Novikoff, N. R. Chowdhury, J. Whiting, A. Reisner, and J. R. Chowdhury, “Survival, organization, and function of microcarrier-attached hepatocytes transplanted in rats,” Proc. Natl. Acad. Sci. USA, Vol.83, No.19, pp. 7475-7479, 1986.
  13. [13] J. Mei, A. Sgroi, G. Mai, R. Baertschiger, C. Gonelle-Gispert, V. Serre-Beinier, P. Morel, and L. H. Buhler, “Improved survival of fulminant liver failure by transplantation of microencapsulated cryopreserved porcine hepatocytes in mice,” Cell Transplant, Vol.18, No.1, pp. 101-110, 2009.
  14. [14] K. Ohashi, F. Park, and M. A. Kay, “Hepatocyte transplantation: clinical and experimental application,” J.Mol. Med., Vol.79, No.11, pp. 617-630, 2001.
  15. [15] A. Kamiya, T. Kinoshita, Y. Ito, T. Matsui, Y. Morikawa, E. Senba, K. Nakashima, T. Taga, K. Yoshida, T. Kishimoto, and A. Miyajima, “Fetal liver development requires a paracrine action of oncostatin M through the gp130 signal transducer,” EMBO J., Vol.18, No.8, pp. 2127-2136, 1999.
  16. [16] A. Kamiya, T. Kinoshita, and A. Miyajima, “Oncostatin Mand hepatocyte growth factor induce hepatic maturation via distinct signaling pathways,” FEBS Lett., Vol.492, No.1-2, pp. 90-94, 2001.
  17. [17] A. Kamiya, N. Kojima, T. Kinoshita, Y. Sakai, and A. Miyaijma, “Maturation of fetal hepatocytes in vitro by extracellular matrices and oncostatin M: induction of tryptophan oxygenase,” Hepatology, Vol.35, No.6, pp. 1351-1359, 2002.
  18. [18] N. Kojima, T. Kinoshita, A. Kamiya, K. Nakamura, K. Nakashima, T. Taga, and A. Miyajima, “Cell density-dependent regulation of hepatic development by a gp130-independent pathway,” Biochem. Biophys. Res. Commun., Vol.277, No.1, pp. 152-158, 2000.
  19. [19] N. Tanimizu, M. Nishikawa, H. Saito, T. Tsujimura, and A. Miyajima, “Isolation of hepatoblasts based on the expression of Dlk/Pref-1,” J. Cell Sci., Vol.116, Pt.9, pp. 1775-1786, 2003.
  20. [20] N. Tanimizu, H. Saito, K. Mostov, and A. Miyajima, “Long-term culture of hepatic progenitors derived from mouse Dlk+ hepatoblasts,” J. Cell Sci., Vol.117, Pt.26, pp. 6425-6434, 2004.
  21. [21] J. Jiang, N. Kojima, L. Guo, K. Naruse,M.Makuuchi, A.Miyajima, W. Yan, and Y. Sakai, “Efficacy of engineered liver tissue based on poly-L-lactic acid scaffolds and fetal mouse liver cells cultured with oncostatin M, nicotinamide, and dimethyl sulfoxide,” Tissue Eng., Vol.10, No.9-10, pp. 1577-1586, 2004.
  22. [22] J. Jiang, N. Kojima, T. Kinoshita, A. Miyajima, W. Yan, and Y. Sakai, “Cultivation of fetal liver cells in a three-dimensional poly-L-lactic acid scaffold in the presence of oncostatin M,” Cell Transplant, Vol.11, No.5, pp. 403-406, 2002.
  23. [23] Y. Sakai, J. Jiang, N. Kojima, T. Kinoshita, and A. Miyajima, “Enhanced in vitro maturation of fetal mouse liver cells with oncostatin M, nicotinamide, and dimethyl sulfoxide,” Cell Transplant, Vol.11, No.5, pp. 435-441, 2002.
  24. [24] Y. S. Nam, J. J. Yoon, and T. G. Park, “A novel fabrication method of macroporous biodegradable polymer scaffolds using gas foaming salt as a porogen additive,” J. Biomed. Mater. Res., Vol.53, No.1, pp. 1-7, 2000.
  25. [25] A. Suzuki, Y. Zheng, R. Kondo, M. Kusakabe, Y. Takada, K. Fukao, H. Nakauchi, and H. Taniguchi, “Flow-cytometric separation and enrichment of hepatic progenitor cells in the developing mouse liver,” Hepatology, Vol.32, No.6, pp. 1230-1239, 2000.
  26. [26] S. Brill, I. Zvibel, and L. M. Reid, “Maturation-dependent changes in the regulation of liver-specific gene expression in embryonal versus adult primary liver cultures,” Differentiation, Vol.59, No.2, pp. 95-102, 1995.
  27. [27] F. Lemaigre and K. S. Zaret, “Liver development update: new embryo models, cell lineage control, and morphogenesis,” Curr. Opin. Genet. Dev., Vol.14, No.5, pp. 582-590, 2004.
  28. [28] R. Zhao and S. A. Duncan, “Embryonic development of the liver,” Hepatology, Vol.41, No.5, pp. 956-967, 2005.
  29. [29] A. Banas, G. Quinn, Y. Yamamoto, T. Teratani, and T. Ochiya, “Stem cells into liver – basic research and potential clinical applications,” Adv. Exp. Med. Biol., Vol.585, pp. 3-17, 2006.
  30. [30] A. Banas, Y. Yamamoto, T. Teratani, and T. Ochiya, “Stem cell plasticity: learning from hepatogenic differentiation strategies,” Dev. Dyn., Vol.236, No.12, pp. 3228-3241, 2007.
  31. [31] K. Takahashi, K. Tanabe, M. Ohnuki, M. Narita, T. Ichisaka, K. Tomoda, and S. Yamanaka, “Induction of pluripotent stem cells from adult human fibroblasts by defined factors,” Cell, Vol.131, No.5, pp. 861-872, 2007.
  32. [32] K. Takahashi and S. Yamanaka, “Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors,” Cell, Vol.126, No.4, pp. 663-676, 2006.
  33. [33] H. Liu, Z. Ye, Y. Kim, S. Sharkis, and Y. Y. Jang, “Generation of endoderm-derived human induced pluripotent stem cells from primary hepatocytes,” Hepatology, Vol.51, No.5, pp. 1810-1819, 2010.
  34. [34] S. T. Rashid, S. Corbineau, N. Hannan, S. J. Marciniak, E. Miranda, G. Alexander, I. Huang-Doran, J. Griffin, L. Ahrlund-Richter, J. Skepper, R. Semple, A. Weber, D. A. Lomas, and L. Vallier, “Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells,” J. Clin. Invest., Vol.120, No.9, pp. 3127-3136, 2010.
  35. [35] K. Si-Tayeb, F. K. Noto, M. Nagaoka, J. Li, M. A. Battle, C. Duris, P. E. North, S. Dalton, and S. A. Duncan, “Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells,” Hepatology, Vol.51, No.1, pp. 297-305, 2010.
  36. [36] Z. Song, J. Cai, Y. Liu, D. Zhao, J. Yong, S. Duo, X. Song, Y. Guo, Y. Zhao, H. Qin, X. Yin, C. Wu, J. Che, S. Lu, M. Ding, and H. Deng, “Efficient generation of hepatocyte-like cells from human induced pluripotent stem cells,” Cell Res., Vol.19, No.11, pp. 1233-1242, 2009.
  37. [37] H. Gai, D. M. Nguyen, Y. J. Moon, J. R. Aguila, L. M. Fink, D. C. Ward, and Y. Ma, “Generation of murine hepatic lineage cells from induced pluripotent stem cells,” Differentiation, Vol.79, No.3, pp. 171-181, 2010.
  38. [38] M. Iwamuro, T. Komaki, Y. Kubota, M. Seita, H. Kawamoto, T. Yuasa, J. M. Shahid, R. A. Hassan, W. A. Hassan, S. Nakaji, Y. Nishikawa, E. Kondo, K. Yamamoto, I. J. Fox, and N. Kobayashi, “Hepatic differentiation of mouse iPS cells in vitro,” Cell Transplant, Vol.19, No.6, pp. 841-847, 2010.
  39. [39] W. Li, D. Wang, J. Qin, C. Liu, Q. Zhang, X. Zhang, X. Yu, B. T. Lahn, F. F. Mao, and A. P. Xiang, “Generation of functional hepatocytes from mouse induced pluripotent stem cells,” J. Cell Physiol., Vol.222, No.3, pp. 492-501, 2010.
  40. [40] P. Sancho-Bru, P. Roelandt, N. Narain, K. Pauwelyn, T. Notelaers, T. Shimizu, M. Ott, and C. Verfaillie, “Directed differentiation of murine-induced pluripotent stem cells to functional hepatocyte-like cells,” J. Hepatol., Vol.54, No.1, pp. 98-107, 2011.

*This site is desgined based on HTML5 and CSS3 for modern browsers, e.g. Chrome, Firefox, Safari, Edge, Opera.

Last updated on Jul. 12, 2024