Skip to main content
PMC home page
Journal of Cellular and Molecular Medicine logoLink to Journal of Cellular and Molecular Medicine
. 2007 May 1;10(3):577–587. doi: 10.1111/j.1582-4934.2006.tb00422.x

Fetal and adult liver stem cells for liver regeneration and tissue engineering

H C Fiegel a,*, Claudia Lange b, U Kneser c, W Lambrecht a, A R Zander b, X Rogiers d, D Kluth a
PMCID: PMC3933144  PMID: 16989722

Abstract

For the development of innovative cell-based liver directed therapies, e.g. liver tissue engineering, the use of stem cells might be very attractive to overcome the limitation of donor liver tissue. Liver specific differentiation of embryonic, fetal or adult stem cells is currently under investigation. Different types of fetal liver (stem) cells during development were identified, and their advantageous growth potential and bipotential differentiation capacity were shown. However, ethical and legal issues have to be addressed before using fetal cells. Use of adult stem cells is clinically established, e.g. transplantation of hematopoietic stem cells. Other bone marrow derived liver stem cells might be mesenchymal stem cells (MSC). However, the transdifferentiation potential is still in question due to the observation of cellular fusion in several in vivo experiments. In vitro experiments revealed a crucial role of the environment (e.g. growth factors and extracellular matrix) for specific differentiation of stem cells. Co-cultured liver cells also seemed to be important for hepatic gene expression of MSC. For successful liver cell transplantation, a novel approach of tissue engineering by orthotopic transplantation of gel-immobilized cells could be promising, providing optimal environment for the injected cells. Moreover, an orthotopic tissue engineering approach using bipotential stem cells could lead to a repopulation of the recipients liver with healthy liver and biliary cells, thus providing both hepatic functions and biliary excretion. Future studies have to investigate, which stem cell and environmental conditions would be most suitable for the use of stem cells for liver regeneration or tissue engineering approaches.

Keywords: fetal stem cells, liver stem cells, mesenchymal stem cells, stem cell culture, liver cell transplantation, hepatic tissue engineering

References

  • 1.Keefee EB. Liver transplatation: Current status and novel approaches to liver replacement. Gastroenterology. 2001;120:749–62. doi: 10.1053/gast.2001.22583. [DOI] [PubMed] [Google Scholar]
  • 2.Banco P, Robey PG. Stem cells in tissue engineering. Nature. 2001;414:118–21. doi: 10.1038/35102181. [DOI] [PubMed] [Google Scholar]
  • 3.Malhi H, Gupta S. Hepatocyte transplantaton: new horizons and challenges. J Hepathobiliary Pancreat Surg. 2001;8:40–50. doi: 10.1007/s005340170049. [DOI] [PubMed] [Google Scholar]
  • 4.Kaufmann PM, Sano K, Uyama S, Schloo B, Vacanti JP. Heterotopic hepatocyte transplantation using three-dimensional polymers: evaluation of the stimulaory effects by portocaval shunt or islet cell cotransplatation. Transplant Proc. 1994;26:3343–5. [PubMed] [Google Scholar]
  • 5.Mooney D, Hansen L, Vacanti J, Langer R, Farmer S, Ingber D. Switching from differentiation to growth in hepatocytes: Control by extracellular matrix. J Cell Physiol. 1992;151:497–505. doi: 10.1002/jcp.1041510308. [DOI] [PubMed] [Google Scholar]
  • 6.Monney DJ, Park S, Kaufmann PM, Sano K, McNamara K, Vacanti JP, Langer R. Biodegradable sponges for hepatocyte transplantation. J. Biomed Mater Res. 1995;29:959–65. doi: 10.1002/jbm.820290807. [DOI] [PubMed] [Google Scholar]
  • 7.Kaufmann PM, Heimrath S, Kim BD, Mooney DJ. Highly porous polymer matrices as three dimensional culture system for hepatocytes. Cell Transplant. 1997;6:463–8. doi: 10.1177/096368979700600505. [DOI] [PubMed] [Google Scholar]
  • 8.Lee H, Cusick RA, Browne F, Kim TH, Ma PX, Utsunomiya H, Langer R, Vacanti JP. Local delivery of basic fibroblast growth factor increases both angiogenesis and engraftment of hepatocytes in tissue-engineered polymer devices. Transplantation. 2002;73:1589–93. doi: 10.1097/00007890-200205270-00011. [DOI] [PubMed] [Google Scholar]
  • 9.Fiegel HC, Havers J, Kneser U, Smith MK, Moeller T, Kluth D, Mooney DJ, Rogiers X, Kaufmann PM. Influence of flow conditions and matrix coatings on growth and differentiation of three-dimensionally cultured rat hepatocytes. Tissue Eng. 2004;10:165–74. doi: 10.1089/107632704322791817. [DOI] [PubMed] [Google Scholar]
  • 10.Kneser U, Kaufmann PM, Fiegel HC, Pollok JM, Kluth D, Herbst H, Rogiers X. Heterotopic hepatocyte transplantation utilizing pancreatic islet cotransplantation for hepatotrophic stimulation: morphologic and morphometric evalluation. Pediatr Surg Int. 1999;15:168–74. doi: 10.1007/s003830050547. [DOI] [PubMed] [Google Scholar]
  • 11.Uyama S, Kaufmann PM, Takeda T, Vacanti JP. Delivery of whole liver-equivalent hepatocyte mass using polymer devices and hepatotrophic stimulation. Transplatation. 1993;55:932–5. doi: 10.1097/00007890-199304000-00044. [DOI] [PubMed] [Google Scholar]
  • 12.Kneser U, Kaufmann PM, Fegel HC, Pollok JM, Kluth D, Herbst H, Rogiers X. Long-term differentated function of heterotopically transplated hepatocytes on three dimensonal polymer matrices. J Biomed Mater Res. 1999;47:494. doi: 10.1002/(sici)1097-4636(19991215)47:4<494::aid-jbm5>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  • 13.Asonuma K, Gilbert JC, Stein JE, Takeda T, Vacanti JP. Quantitation of transplanted hepatic mass necessary to cure the Gunn rat model of hyperbilirebinemia. J Pediatr Surg. 1992;27:298–301. doi: 10.1016/0022-3468(92)90850-7. [DOI] [PubMed] [Google Scholar]
  • 14.Uyama S, Kaufmann PM, Kneser U, Fiegel HC, Pollok JM, Kluth D, Vacanti JP, Rogiers X. Hepatocyte transplantation using biodegradable matrces in ascorbic acid-deficient rats: comparision with heterotopically transplanted liver graft. Transplant. 2001;71:1226–31. doi: 10.1097/00007890-200105150-00008. [DOI] [PubMed] [Google Scholar]
  • 15.Suzuki A, Zheng YW, Kondo R, Kusakabe M, Tkada Y, Fukao K, Nakauch H, Taniguchi H. Flowcytometric separation and enrichment of hepatic progenitor cells in the developing mouse liver. Hepatology. 2000;32:1230–9. doi: 10.1053/jhep.2000.20349. [DOI] [PubMed] [Google Scholar]
  • 16.Taniguchi H, Suzui A, Zheng Y, Kondo R, Takada Y, Fukunaga K, Seino K, Yuzawa K, Otsuka M, Fukao, Nakauchi H. Usefulness of flowcytometric cell sorting for the enrichment of hepatic stem and progenitor cells in the liver. Transplant Proc. 2000;32:249–51. doi: 10.1016/s0041-1345(99)00947-1. [DOI] [PubMed] [Google Scholar]
  • 17.Suzuki A, Zheng YW, Kaneko S, Onodera M, Kukao K, Nakauchi H, Taniguchi H. Clonal identification and characterization of self-renewing pluripotent stem cells in the developing liver. J Cell Biol. 2002;156:173–84. doi: 10.1083/jcb.200108066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Dabeva MD, Petkov PM, Sandhu J, Oren R, Laconi E, Hurston E, Shafritz DA. Proliferation and differentation of fetal liver epithelial progenitor cells after transplantation in the rat liver. Am J. Pathol. 2000;156:2017–31. doi: 10.1016/S0002-9440(10)65074-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Sandhu JS, Petkov PM, Dabeva MD, Shafritz DA. Stem cell properties and repopulation of the rat liver by fetal lever epithelial progenitor cells. Am J Pathol. 2001;159:1323–34. doi: 10.1016/S0002-9440(10)62519-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Nierhoff D, Ogawa A, Oertel M, Chen YQ, Shafritz DA. Purification and chracterization of mouse fetal liver epithelial cells with high in vivo repopulation capacity. Hepatology. 2005;42:130–9. doi: 10.1002/hep.20735. [DOI] [PubMed] [Google Scholar]
  • 21.Fiegel HC, Park JH, Lioznov MV, Martin A, Jaeschke-Melli S, Kaufmann PM, Fehse B, Zander AR, Kluth D. Characterization of cell types during rat liver development. Hepatology. 2003;37:148–54. doi: 10.1053/jhep.2003.50007. [DOI] [PubMed] [Google Scholar]
  • 22.Thorgeirsson SS. Liver regeneration 9: Hepatic Stem cells in liver regeneration. FASEB J. 1996;10:1249–56. [PubMed] [Google Scholar]
  • 23.Miichalopoulos GK, DeFrances MC. Liver regeneration. Science. 1997;276:60–6. doi: 10.1126/science.276.5309.60. [DOI] [PubMed] [Google Scholar]
  • 24.Strain AJ, Crosby HA. Hepatic stem cells. Gut. 2000;46:743–5. doi: 10.1136/gut.46.6.743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Vessey C, de la Hall PM. Hepatic stem cells. Pathology. 2001;33:130–41. [PubMed] [Google Scholar]
  • 26.Haruna Y, Saito K, Spaulding S, Nalesnik MA, Gerber MA. Identification of bipotential progenitor cells in human liver development. Hepatology. 1996;23:476–81. doi: 10.1002/hep.510230312. [DOI] [PubMed] [Google Scholar]
  • 27.Lazaro CA, Rhim JA, Yamada Y, Fausto N. Generation of hepatiocytes from oval cell precursors in culture. Cancer Res. 1998;58:5514–22. [PubMed] [Google Scholar]
  • 28.Evarts RP, Nagy P, Marsden E, Thorgeirsson SS. A precursor-product relationship exists between oval cells and hepatocytes in rat liver. Carcinogenesis. 1993;8:1737–40. doi: 10.1093/carcin/8.11.1737. [DOI] [PubMed] [Google Scholar]
  • 29.Thorgeirsson SS, Evarts RP, Bisgaard HC, Flujio K, Hu Z. Hepatic stem cell compartment: activation and lineage commitment. Proc Soc Exp Biol Med. 1993;204:253–60. doi: 10.3181/00379727-204-43661. [DOI] [PubMed] [Google Scholar]
  • 30.Petersen BE, Zajak VF, Michalopoulos GK. Hepatic oval cell activation in resopnse to injury following chemically induced periportal or pericentral damage in rats. Hepatology. 1998;27:1030–8. doi: 10.1002/hep.510270419. [DOI] [PubMed] [Google Scholar]
  • 31.Fiegel HC, Kluth J, Lioznov MV, Holzhuter S, Fehse B, Zander AR, Kluth D. Hepatic lineages isolated from developing rat liver show differents ways of maturation. Biolchem Biophys Res Comm. 2003;305:46–53. doi: 10.1016/s0006-291x(03)00662-4. [DOI] [PubMed] [Google Scholar]
  • 32.Fiegel HC, Bruns H, Hoper C, Lioznov MV, Kluth D. Cell growth and differentiation of different hepatic cells isolated from fetal rat livers in vitro. Tissue Eng. 2006;12:123–30. doi: 10.1089/ten.2006.12.123. [DOI] [PubMed] [Google Scholar]
  • 33.McLaren A. Ethical and social considerations of stem cell research. Nature. 2001;414:129–31. doi: 10.1038/35102194. [DOI] [PubMed] [Google Scholar]
  • 34.Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, Boggs SS, Greenberger JS, Goff JP. Bone marrow as a potential Source of hepatic oval cells. Science. 1999;284:1168–70. doi: 10.1126/science.284.5417.1168. [DOI] [PubMed] [Google Scholar]
  • 35.Theise ND, Badve S, Saxena R, Henegariu O, Sell S, Crawford JM, Krause DS. Derivation of hepatocytes from bone marrow cells in mice after radiation induced myeloablation. Hepatology. 2000;31:235–40. doi: 10.1002/hep.510310135. [DOI] [PubMed] [Google Scholar]
  • 36.Alison MR, Poulsom R, Jeffery R, Dhillon AP, Quaglia A, Jacob J, Novelli M, Prentice G, Williamson J, Wright NA. Hepatocytes from non-hepatic adult stem cells. Nature. 2000;406:257. doi: 10.1038/35018642. [DOI] [PubMed] [Google Scholar]
  • 37.Theise ND, Nimmakayalu M, Gardner R, Ille PB, Morgan G, Teperman L, Henegariu O, Krause D. Liver from bone marrow in humans. Hepatology. 2000;32:11–6. doi: 10.1053/jhep.2000.9124. [DOI] [PubMed] [Google Scholar]
  • 38.Korbling M, Katz RL, Khanna A, Ruifrok AC, Rondon G, Albitar M, Champlin RE, Estrov Z. Hepatocytes and epithelial cells of donor orighin in the recipients of peripheral blood stem cell transplantation. N Engl J Med. 2002;346:738–46. doi: 10.1056/NEJMoa3461002. [DOI] [PubMed] [Google Scholar]
  • 39.Lagasse E, Connors H, Al-Dhalimy M, Retsma M, Dohse M, Osborne L, Wang X, Finegold M, Weissman IL, Grompe M. Purified hematopoietic stem cells cen differentiate into hepatocytes. in vivo. Nature Med. 2000;6:1229–34. doi: 10.1038/81326. [DOI] [PubMed] [Google Scholar]
  • 40.Wang X, Willenbring H, Akkari Y, Torimaru Y, Foster M, Al-Dhalimy M, Lagasse E, Finegold M, Olson S, Grompe M. Cell fusion is the principal source of bone marrow derived hepatocytes. Nature. 2003;422:897–901. doi: 10.1038/nature01531. [DOI] [PubMed] [Google Scholar]
  • 41.Vassilopoulos G, Wang PR, Russell DW. Transplanted bone marrow regenerates liver by cell fusion. Nature. 2003;422:901–4. doi: 10.1038/nature01539. [DOI] [PubMed] [Google Scholar]
  • 42.Wang X, Ge S, McNamara G, Hao QL, Crooks GM, Nolta JA. Albumn-expressing hepatocyte-like cells develop in the livers of immune-deficient mice that received transplants of highly purified human Hematopoietic stem cells. Blood. 2003;101:4201–8. doi: 10.1182/blood-2002-05-1338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Ishikawa F, Drake CJ, Yang S, Fleming P, Minamiguchi H, Visconti RP, Crosby CV, Argraves WS, Harada M. Key LL, Jr, Livingston AG, Wingard JR, Ogawa M. Transplanted human cord blood cells give rise to hepatocytes in engrafted mice. Ann N Y Acad Sci. 2003;996:174–85. doi: 10.1111/j.1749-6632.2003.tb03245.x. [DOI] [PubMed] [Google Scholar]
  • 44.Newsome PN, Johannessen I, Boyle S, Dalakas E, McAulay KA, Samuel K, Rae F, Forrester L, Turner ML, Hayes PC, Harrison DJ, Bickmore WA, Plevris JN. Human cord blood-derived cells can differentiate into hepatocytes in the mouse liver with no evidence of cellular fusion. Gastroenteroology. 2003;124:1891–900. doi: 10.1016/s0016-5085(03)00401-3. [DOI] [PubMed] [Google Scholar]
  • 45.Oh SH, Miyazaki M, Kouchi H, Inoue Y, Sakaguchi M, Tsuji T, Shima N, Higashio K, Namba M. Hepatocyte growth factor induces differentiation of adult rat bone marrow cells into hepatocyte lineage. in vitro. Biochem Biophys Res Comm. 2000;279:500–4. doi: 10.1006/bbrc.2000.3985. [DOI] [PubMed] [Google Scholar]
  • 46.Fiegel HC, Lioznov MV, Cortes-Dericks L, Lange C, Kluth D, Fehse B, Zander AR. Liver specific gene expression in cultured human hematopoietic stem cells. Stem Cells. 2003;21:98–104. doi: 10.1634/stemcells.21-1-98. [DOI] [PubMed] [Google Scholar]
  • 47.Kakinuma S, Tanaka Y, Chinzei R, Watanabe M, Shimizu-Saito K, Hara Y, Teramoto K, Arii S, Sato C, Takase K, Yasumizu T, Teraoka H. Human umbilical cord blood as source of transplantable hepatic progenitor cells. Stem Cells. 2003;21:217–27. doi: 10.1634/stemcells.21-2-217. [DOI] [PubMed] [Google Scholar]
  • 48.Schwartz RE, Reyes M, Koodie L, Jiang Y, Blackstad M, Lund T, Lenvik T, Johnson S, Hu WS, Verfaillie CM. Multipotent adult progenitor cells from bone marrw differentiate into functional hepatocyte-like cells. J Clin Invest. 2002;109:1291–302. doi: 10.1172/JCI15182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Block GD, Locker J, Bowen WC, Petersen BE, Katyal S, Strom SC, Riley T, Howard TA, Michalopoulos GK. Population expansion, clonal growth, and specific differentiation patterns in primary cultures of hepatocytes induced by HGF/SF, EGF, and TGF alpha in an chemically defined (HGM) medium. J Cell Biol. 1996;132:1133–49. doi: 10.1083/jcb.132.6.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Reid LM. Stem cell biology, hormone/matrix synergies and liver differentiation. Curr Opin Cell Biol. 1990;2:121–30. doi: 10.1016/s0955-0674(05)80042-0. [DOI] [PubMed] [Google Scholar]
  • 51.Berthiaume F, Moghe PV, Toner M, Yarmush ML. Effect of extracellular matrix topology on cell structure, function, and physiological responsiveness: hepatocytes cultured in a sandwich configuration. FASEB J. 1996;10:1471–84. doi: 10.1096/fasebj.10.13.8940293. [DOI] [PubMed] [Google Scholar]
  • 52.Guguen-Guillouzo C, Clement B, Baffet G, Beaumont C, Morel-Chany E, Glaise D, Guillouzo A. Maintenance and reversibility of active albumin secretion by adult rat hepatocytes co-cultured with another liver epithelial cell type. Exp Cell Res. 1983;143:47–54. doi: 10.1016/0014-4827(83)90107-6. [DOI] [PubMed] [Google Scholar]
  • 53.Shimaoka S, Nakamura T, Ichihara A. Stimulation of growth of primary cultured adult rat hepatocytes without growth factors by coculture with nonparenchymal liver cells. Exp Cell Res. 1987;172:228–42. doi: 10.1016/0014-4827(87)90109-1. [DOI] [PubMed] [Google Scholar]
  • 54.Miyazaki M, Akiyama I, Sakaguchi M, Nakashima E, Okada M, Kataoka K, Huh NH. Improved conditions to induce hepatocytes from rat bone marrow cells in culture. Biochem Biophys Res Comm. 2002;298:24–30. doi: 10.1016/s0006-291x(02)02340-9. [DOI] [PubMed] [Google Scholar]
  • 55.Avital I, Inderbitzin D, Aoki T, Tyan DB, Cohen AH, Ferraresso C, Rozga J, Arnaout WS, Demetriou AA. Isolation, characterization, and transplantation of bone marrow derived hepatocyte stem cells. Biochem Biophys Res Comm. 2001;288:156–64. doi: 10.1006/bbrc.2001.5712. [DOI] [PubMed] [Google Scholar]
  • 56.Okumoto K, Saito T, Hattori E, Ito JI, Adachi T, Takeda T, Sugahara K, Watanabe H, Saito K, Togashi H, Kawata S. Differentiation of bone marrow cells into cells that express liver-specific genes in vitro: implication of the Notch signals in differentiation. Biochem Biophys Res Comm. 2003;304:691–5. doi: 10.1016/s0006-291x(03)00637-5. [DOI] [PubMed] [Google Scholar]
  • 57.Lange C, Bassler P, Lioznov MV, Bruns H, Kluth D, Zander AR, Fiegel HC. Hepatocytic gene expression in cultured rat mesenchymal stem cells. Transplant Proc. 2005;37:276–9. doi: 10.1016/j.transproceed.2004.11.087. [DOI] [PubMed] [Google Scholar]
  • 58.Lange C, Bassler P, Lioznov MV, Bruns H, Kluth D, Zander AR, Fiegel HC. Liver-specific gene expression in mesenchymal stem cells is induced by liver cells. World J Gastroenterol. 2005;11:4497–504. doi: 10.3748/wjg.v11.i29.4497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 59.Wulf GG, Luo KL, Jackson KJA, Brenner MK, Goodell MA. Cells of the hepatic side population contribute to liver regeneration and can be replenished by bone marrow stem cells. Haematologica. 2003;88:368–78. [PubMed] [Google Scholar]
  • 60.Shu SN, Wei L, Wang JH, Zhan YT, Chen HS, Wang Y. Hepatic differentiation capability of rat bone marrow-derived mesenchymal stem cells and hematpoietic stem cells. World J Gastroenterol. 2004;10:2818–22. doi: 10.3748/wjg.v10.i19.2818. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61.Kang XQ, Zang WJ, Song TS, Xu XL, Yu XJ, Li DL, Meng KW, Wu SL, Zhao ZY. Rat bone marrow mesenchymal stem cells differentiate into hepatocytes. in vitro. World J Gastroenterol. 2005;11:3479–84. doi: 10.3748/wjg.v11.i22.3479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62.Lee KD, Kuo TK, Whang-Peng J, Chung YF, Lin CT, Chou SH, Chen JR, Chen YP, Lee OK. In vitro hepatic differentiation of humen mesenchymal stem cells. Hepatology. 2004;40:1275–84. doi: 10.1002/hep.20469. [DOI] [PubMed] [Google Scholar]
  • 63.Mitaka T. Hepatic stem cells: from bone marrow cells to hepatocytes. Biochem Biophys Res Comm. 2001;281:1–5. doi: 10.1006/bbrc.2001.4270. [DOI] [PubMed] [Google Scholar]
  • 64.Mitaka T. Reconstruction of hepatic organoid by hepatic stem cells. J Hepatobiliary Panceat Surg. 2002;9:697–703. doi: 10.1007/s005340200096. [DOI] [PubMed] [Google Scholar]
  • 65.Nakajima Y, Shimamura T, Kamiyama T, Matsushita M, Sato N, Todo S. Control of intraoperative bleeding during liver resection: analysis of a questionaire sent to 231 Japanese hospitals. Surg Today. 2002;32:48–52. doi: 10.1007/s595-002-8112-0. [DOI] [PubMed] [Google Scholar]
  • 66.Ochsner MG, Maniscalco-Theberge ME, Compton HR. Fibrin glue as a hemostatic agent in hepatic and splenic trauma. J Trauma. 1990;30:884–7. doi: 10.1097/00005373-199007000-00020. [DOI] [PubMed] [Google Scholar]
  • 67.Feinstein AJ, Varela JE, Cohn SM, Compton PR, McKenney MG. Fibrin glue eliminates the need for packing after complex liver injuries. Yale J Biol Med. 2001;5:315–21. [PMC free article] [PubMed] [Google Scholar]
  • 68.Xu JW, Zaporojan V, Peretti GM, Roses RE, Morse KB, Roy AK, Mesa JM, Randolph MA, Bonassar LJ, Yaremchuk MJ. Injectable tissue-engineered cartilage with different chondrocyte sources. Plast Reconstr Surg. 2004;113:1361–71. doi: 10.1097/01.prs.0000111594.52661.29. [DOI] [PubMed] [Google Scholar]
  • 69.Wechselberger G, Russell RC, Neumeister MW, Schoeller T, Piza-Katzer H, Rainer C. Successful transplantation of three tissue engineered cell types using capsule induction technique and firbin glue as a delivery vehicle. Plast Reconstr Surg. 2002;110:123–9. doi: 10.1097/00006534-200207000-00022. [DOI] [PubMed] [Google Scholar]
  • 70.Stangenberg L, Schaefer DJ, Buettner O, Ohnolz J, Mobest D, Horch RE, Stark GB, Kneser U. Differentiation of osteoblasts in three-dimensional culture in processed cancellous bone matrix: quantitative analysis of gene expression based on real-time RT-PCR. Tissue Eng. 2005;11:855–64. doi: 10.1089/ten.2005.11.855. [DOI] [PubMed] [Google Scholar]
  • 71.Bruns H, Kneser U, Holzhuter S, Roth B, Kluth J, Kaufmann PM, Kluth D, Fiegel HC. Injectable liver: a novel approach using fibrin gel as a matrix for culture and intrahepatic transplantation of hepatocytes. Tissue Eng. 2005;11:1718–26. doi: 10.1089/ten.2005.11.1718. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Cellular and Molecular Medicine are provided here courtesy of Blackwell Publishing

RESOURCES