Hepatic Tissue Engineering Using Scaffolds: State of the Art


PDF - Export to EndNote - PubMed Central XML format - PubMed Central XML format - PubMed Central XML format
PMID: 23408654 (PubMed) - PMCID: PMC3558138 - View online: PubReader
Volume 1, Issue 3, October-December , Page 135 to 145
Saturday, August 22, 2009 :Received , Wednesday, October 28, 2009 :Accepted


  • Corresponding author Ph.D., Department of Embryology and Stem Cells, Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran, P.O. Box: 19615-1177, Tel: +98 21 22432020, Fax: +98 21 22432021, E-mail: kazemnejad_s@yahoo.com
    - Department of Embryology and Stem Cells, Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR , Tehran, Iran

Abstract:

Severe hepatic failure accounts for many deaths and raises medical costs each year worldwide. Currently, liver transplantation is the most common therapeutic option for patients with end-stage chronic liver disease. Due to decrease in the number of organ donors, many in need of transplantation continue to remain on the waiting list. Hepatic Tissue Engineering is a step toward alleviating the need for organ donors. Regenerative medicine and tissue engineering require two complementary key ingredients as follows: 1) biologically compatible scaffolds that can be readily adopted by the body system without harm, and 2) suitable cells including various stem cells or primary cells that effectively replace the damaged tissues without adverse consequences. Yet many challenges must be overcome such as scaffold choice, cell source and immunological barriers. Today, hepatogenic differentiation of stem cells has created trust and promise for use of these cells in hepatic tissue engineering and liver replacement. However, using suitable scaffolds is an important key to achieving the necessary functions required for hepatic replacement. In recent years, different scaffolds have been used for liver tissue engineering. In this review, we have presented different concepts in using cell /scaffold constructs to guide hepatic tissue engineering.


 

 


Introduction :
Every year, the number of patients needing a hepatic transplant increases. Many of those in need of a transplant have suffered from full hepatic failure caused by disease, genetic complications or adverse drug reactions. Cur-rently, there are many people waiting to have a liver transplant. However, there are not enough organ donors.
At the moment, there are about 700 patients waiting to have a liver transplant in Iran, but the number of liver donors is less than 200. At present, liver transplantation is the only therapeutic option for patients with end-stage chronic liver disease and severe liver failure.
However, the efficacy of liver transplantation is limited by the shortage of available organ donors, risk of rejection, infections, and other complications caused by the lifelong immunosuppression (1).
Tissue engineering proves to be a tem-porary treatment for patients suffering from hepatic failure (2). For successful tissue regen-eration, the cells constituting tissues to be re-generated are necessary. Considering the pro-liferation activity and differentiation potential of cells, stem cells are practically promising. Self-renewal is a unique property of stem cells that gives multi-potential differentiation ability to them.
Today, there are different studies showing hepatogenic differentiation capacity of the stem cells (3-5). However, the challenge re-mains to develop robust protocols, to generate functional hepatocytes from stem cells suit-able for the transplantation.
A complementary key ingredient in regen-erative medicine and tissue engineering is to make a use of biologically compatible scaf-folds that can be readily adopted by the body system without harm (6). Advances in polymer chemistry have facilitated the engineering of synthetic matrices that can be precisely ma-nipulated with regard to physical and mechan-ical characteristics. This review has presented some directions that the field of liver tissue engineering is heading.

Hepatic biology
The liver is a highly metabolic, complex array of vasculature, endothelial cells and parenchymal cells that performs many func-tions in the body. The bulk of the liver is primarily composed of parenchymal cells such as hepatocytes, hepatocyte precursor cells (oval cells or Ito cells), stellate cells, kuppfer cells, epithelial cells, sinusoidal epi-thelial cells, biliary epithelial cells and fibro-blasts (7). Hepatocytes constitute approximate-ly 70% of the cellular population of the liver and perform major metabolic functions such as plasma protein synthesis and transport, xenobiotic metabolism, glucose homeostasis, urea synthesis, and ketogenesis (8). Thus, hepatocytes used for tissue engineering pur-poses must be able to perform these basic functions.

Cell source
In the field of hepatic tissue engineering, choosing cell type and cell source is important because it is necessary to choose cells that demonstrate the particular phenotype of interest. The various cell types that have been studied include stem cells, hematopoietic cells, oval progenitor cell and mature hepato-cytes (9-11). Deciding which cell type to use is dictated by the need and desire for the cells to perform in a predicted manner, exhibiting certain characteristics.
Hepatic progenitor cells found within the liver have already begun to differentiate, but still have several options before becoming destined to a specific cell line. These cells will not necessary become mature hepato-cytes, but may in fact differentiate into other functional cells of the liver, such as bile duct cells (12,13). Hepatic progenitor cells are often distinguished as primary or small hepatocytes. Mature hepatocytes can be obtained either from the perfusion of an intact or resectioned liver or from an established cell line.
Currently, primary mature hepatocytes, the most common cellular component in current liver tissue engineering, do not replicate suffi-ciently in vitro to meet the requirements of clinical use an

 


Discussion :
With the recent advances in the field of hepatic tissue engineering, there is much promise of working towards an implantable whole organ. Many new polymers are being developed that respond to thermal changes, release imbedded or attached growth factors and other mediators, and have degradation characteristics and properties that is ideal for growth, viability, and attachment. An optimal polymer is being developed based on desired characteristics. Recently, electrospun nano-fibrous scaffolds showed great promise and potential for liver tissue engineering.
Many other factors are being studied that contribute to cell growth and differentiation. However, further studies need to be per-formed for the development of a bioartificial liver system.
With the growth of the tissue-engineering field, many ethical considerations must be recognized. Determining which cell source is safest for patients, which cells should be used, whether they are embryonic stem cells, oval progenitors or adult stem cells, and how the cells should be stored and cultured are im-portant issues to take into consideration.
Hepatic tissue engineering is an ever ex-panding field encompassing and including new areas of study. Because of its multidis-ciplinary nature, it is important for clinicians, basic scientists and engineers to collaborate and explore all areas of possibilities. With each new advance in the field of tissue engin-eering, a step towards an implantable liver is realized. Even though the goal of creating an entire implantable organ has not yet been reached, the progress towards this goal is proving to be fruitful to all those involved, mainly the patients who will benefit from the advancements being made.

 



References :
  1. Kuling KM, Vacanti JP. Hepatic tissue engin-eering. Transpl Immunol 2004;12(3-4):303-310.
  2. Lorenzini S, Andreone P. Stem cell therapy for human liver cirrhosis: a cautious analysis of the results. Stem Cells 2007;25(9):2383-2384.
  3. Di Bonzo LV, Ferrero I, Cravanzola C, Mareschi K, Rustichell D, Novo E, et al. Human mesen-chymal stem cells as a two-edged sword in hepatic regenerative medicine: engraftment and hepatocyte differentiation versus profibrogenic potential. Gut 2008;57(2):153-155.
  4. Lee KD, Kuo TK, Whang-Peng J, Chung YE, Lin CT, Chou SH, et al. In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology 2004;40(6):1275-1284.
  5. Snykers S, Vanhaecke T, De Becker A, Papeleu P, Vinken M, Van Riet I, et al. Chromatin remodeling agent trichostatin A: a key-factor in the hepatic differentiation of human mesenchymal stem cells derived of adult bone marrow. BMC Dev Biol 2007;7:24-39.
  6. Vacanti JP, Langer R, Upton J, Marler JJ. Trans-plantation of cells in matrices for tissue regener-ation. Adv Drug Deliv Rev 1998;33(1-2):165-182.
  7. Arias IM, Boyer JL, Fausto N, Jakoby WB, Scha-chter D, Shafritz DA, et al. The liver: Biology and pathobiology. 4th ed. New York: Raven Press Ltd; 2001,591-610.
  8. Oertel M, Shafritz DA. Stem cells, cell transplan-tation and liver repopulation. Biochim Biophys Acta 2008;1782(2):61-74.
  9. Mitaka T, Mizuguchi T, Sato F, Mochizuki C, Mo-chizuki Y. Growth and maturation of small hepato-cytes. J Gastroenterol Hepatol 1998;13(Suppl):S 70-77.
  10. Allen JW, Bhatia SN. Engineering liver therapies for the future. Tissue Eng 2002;8(5):725-737.
  11. Nyberg SL, Remmel RP, Mann HJ, Peshwa MV, Hu W, Cerra FB, et al. Primary hepatocytes out-perform HepG2 cells as the source of biotrans-formation functions in a bioartificial liver. Ann Surg 1994;220(1):59-67.
  12. Faris RA, Konkin T, Halpert G. Liver stem cells: a potential source of hepatocytes for the treatment of human liver disease. Artif Organs 2001;25(7):513-521.
  13. Noishiki Y. Dreams for the future in the field of in vivo tissue engineering. Artif Organs 2001;25 (3):159-163.
  14. Torok E, Pollok JM, Ma PX, Kaufmann PM, Dan-dri M, Peterson J, et al. Optimization of hepatocyte spheroid formation for hepatic tissue engineering on three-dimensional biodegradable polymer whit in a flow bioreactor prior to implantation. Cells Tissues Organs 2001;169:34-41.
  15. Fausto N. Liver regeneration and repair: hepato-cytes, progenitor cells, and stem cells. Hepatology 2004;39(6):1477-1487.
  16. Shafritz DA, Oertel M, Menthena A, Nierhoff D, Dabeva MD. Liver stem cells and prospects for liver reconstitution by transplanted cells. Hepato-logy 2006;43(2Suppl 1):S89-98.
  17. Grompe M. The role of bone marrow stem cells in liver regeneration. Semin Liver Dis 2003;23(4): 363-372.
  18. Henningson CT, Stanislaus MA, Gewirtz AM. Embryonic and adult stem cell therapy. J Allergy Clin Immunol 2003;111( Suppl 2):S745-753.
  19. Kazemnejad S, Allameh A, Gharehbaghian A, Soleimani M, Amirizadeh N, Jazayeri M. Efficient replacing of fetal bovine serum with human platelet releasate during propagation and differ-entiation of human bone marrow-derived mesenchymal stem cells to functional hepatocytes-like cells. Vox Sang 2008;95(2):149-158.
  20. Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, et al. Bone marrow as a potential source of hepatic oval cells. Science 1999;284(5417):1168-1170.
  21. Allameh A, Esmaeli S, Kazemnejad S, Soleimani M. Differential expression of glutathione S-transferases P1-1 and A1-1 at protein and mRNA levels in hepatocytes derived from human bone marrow mesenchymal stem cells. Toxicol In Vitro 2009;23(4):674-679.
  22. Di Bonzo LV, Ferrero I, Cravanzola C, Mareschi K, Rustichell D, Novo E, et al. Human mesen-chymal stem cells as a two-edged sword in hepatic regenerative medicine: engraftment and hepatocyte differentiation versus profibrogenic potential. Gut 2008;57(2):223-231.
  23. Lee KD, Kuo TK, Whang-Peng J, Chung YE, Lin CT, Chou SH, et al. In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology 2004;40(6):1275-1284.
  24. Snykers S, Vanhaecke T, Becker A, Papeleu P, Vinken M, Van Riet I, et al. Chromatin remodeling agent trichostatin A: a key-factor in the hepatic differentiation of human mesenchymal stem cells derived of adult bone marrow. BMC Develop-mental Biology 2007;7:24-39.
  25. Snykers S, De Kock J, Rogiers V, Vanhaecke T. In vitro differentiation of embryonic and adult stem cells into hepatocytes: State of the art. Stem Cells 2009;27(3):577-605.
  26. Theise ND. Gastrointestinal stem cells. III. Emer-gent themes of liver stem cell biology: niche, qui-escence, self-renewal, and plasticity. Am J Physiol Gastrointest Liver Physiol 2006; 290(2):189-193.
  27. Naveiras O, Daley GQ. Stem cells and their niche: a matter of fate. Cell Mol Life Sci 2006;63(7-8): 760-766.
  28. Benayahu D, Akavia UD, Shur I. Differentiation of bone marrow stroma-derived mesenchymal cells. Curr Med Chem 2007;14(2):173-179.
  29. He XC, Zhang J, Tong WG, Tawfik O, Ross J, Scoville DH, et al. BMP signaling inhibits intes-tinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling. Nat Genet 2004;36 (10):1117-1121.
  30. Moore KA, Lemischka IR. Stem cells and their niches. Science 2006;311(5769):1880-1885.
  31. Shafritz DA, Oertel M, Menthena A, Nierhoff D, Dabeva MD. Liver stem cells and prospects for liver reconstitution by transplanted cells. Hepato-logy 2006;43(2Suppl 1):S89-98.
  32. Fuchs E, Tumbar T, Guasch G. Socializing with the neighbors: stem cells and their niche. Cell 2004;116(6):769-778.
  33. Koller MR, Manchel I, Palsson BO. Importance of parenchymal:stromal cell ratio for the ex vivo reconstitution of human hematopoiesis. Stem Cells 1997;15(4):305-313.
  34. Zhao R, Duncan SA. Embryonic development of the liver. Hepatology 2005;41(5):956-967.
  35. Kinoshita T, Miyajima A. Cytokine regulation of liver development. Biochim Biophys Acta 2002; 1592(3):303-312.
  36. Lemaigre F, Zaret KS. Liver development update: new embryo models, cell lineage control, and morphogenesis. Curr Opin Genet Dev 2004;14(5): 582-590.
  37. Clotman F, Lemaigre FP. Control of hepatic differentiation by activin/ TGF beta signaling. Cell Cycle 2006;5(2):168-171.
  38. Terada S, Sato M, Sevy A, Vacanti JP. Tissue engineering in the twenty-first century. Yonsei Med J 2000;41(6):685-691.
  39. Ong SY, Dai H, Leong KW. Inducing hepatic differentiation of human mesenchymal stem cells in pellet. Biomaterials 2006;27(22):4087-4097.
  40. Schwartz RE, Reyes M, Koodie L, Jiang Y, Blackstad M, Lund T,et al. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J Clin Invest 2002;109(10):1291-1302.
  41. Fiegel HC, Lioznov MV, Cortes-Dericks L, Lange C, Kluth D, Fehse B, et al. Liver-specific gene expression in cultured human hematopoietic stem cells. Stem Cells 2003;21(1):98-104.
  42. Baharvand H, Hashemi SM, Kazemi Ashtiani S, Farrokhi A. Differentiation of human embryonic stem cells into hepatocytes in 2D and 3D culture systems in vitro. Int J Dev Biol 2006;50(7):645-652.
  43. Badylak SF, Freytes DO, Gilbert TW. Extra-cellular matrix as a biological scaffold material: Structure and function. Acta Biomaterialia 2009;5 (1):1-13.
  44. Wong W, Mooney D. Synthesis and properties of biodegradable polymers used as synthetic matrices for tissue engineering. In: Atala A, Mooney D (eds). Synthetic biodegradable polymer scaffolds. Boston, MA: Birkhauser; 1997,51-82.
  45. Zhang YZ, Venugopal J, Huang ZM, Lim CT , Ramakrishn S. Characterization of the surface biocompatibility of the electrospun PCL-collagen nanofibers using fibroblasts. Biomacromolecules 2005;6(5):2583-2589.
  46. Venugopal J, Zhang YZ, Ramakrishna S. Fabri-cation of modified and functionalized polycapro-lactone nanofibre scaffolds for vascular tissue engineering. Nanotechnology 2005;16:2138-2142.
  47. Minuth WW, Sittinger M, Kloth S. Tissue engin-eering: generation of differentiated artificial tissues for biomedical applications. Cell Tissue Res 1998; 291(1):1-11.
  48. Hosseinkhani H, Hosseinkhani M, Tian F, Koba-yashi H, Tabata Y. Ectopic bone formation in col-lagen sponge self-assembled peptide-amphiphile nanofibers hybrid scaffold in a perfusion culture bioreactor. Biomaterials 2006;27(29):5089-5098.
  49. Hosseinkhani H, Hosseinkhani M, Tian F, Kobayashi H, Tabata Y. Osteogenic differentiation of mesenchymal stem cells in self-assembled pep-tide-amphiphile nanofibers. Biomaterials 2006;27 (22):4079-4086.
  50. Mohammadi Y, Soleimani M, Fallahi-Sichani M, Gazme A, Haddadi-Asl V, Arefian E, et al. Nano-fibrous poly (epsilon-caprolactone)/ poly (vinyl alcohol)/ chitosan hybrid scaffolds for bone tissue engineering using mesenchymal stem cells. Int J Artif Organs 2007;30(3):204-211.
  51. Xin X, Hussain M, Mao JJ.Continuing differenti-ation of human mesenchymal stem cells and induced chondrogenic and osteogenic lineages in electrospun PLGA nanofiber scaffold. Biomater-ials 2007;28(2):316-325.
  52. Shih YR, Chen CN, Tsai SW, Wang YJ, Lee OK. Growth of mesenchymal stem cells on electrospun type I collagen nanofibers. Stem Cells 2006;24 (11):2391-2397.
  53. Smith LA, Ma PX. Nano-fibrous scaffolds for tissue engineering. Colloids Surf B Biointerfaces 2004;39(3):125-131.
  54. Li WJ, Laurencin CT, Caterson EJ, Tuan RS, Ko FK. Electrospun nanofibrous structure: a novel scaffold for tissue engineering. J Biomed Mater Res 2002;60(4):613-621.
  55. Li M, Guo Y, Wei Y, MacDiarmid AG, Lelkes PI. Electrospinning polyaniline-contained gelatin nanofibers for tissue engineering applications. Biomaterials 2006;27(13):2705-2715.
  56. Kazemnejad S, Allameh A, Soleimani M, Ghareh-baghian A, Mohammadi Y, Amirizadeh N, et al. Development of a novel three-dimensional bio-compatible nanofibrous scaffold for the expansion and hepatogenic differentiation of human bone marrow mesenchymal stem cells. Iran J Biotechnol 2007;5(4):201-211.
  57. Glicklis R, Shapiro L, Agbaria R, Merchuk JC, Cohen S. Hepatocyte behavior within three dimen-sional porous alginate scaffolds. Biotechnol Bio-eng 2000;67(3):344-353.
  58. Hamamoto R, Yamada K, Kamihira M, Iijima S. Differentiation and proliferation of primary rat hepatocytes cultured as spheroids. J Biochem 1998;124(5):972-979.
  59. Landry J, Bernier D, Ouellet C, Goyette R, Mar-ceau N. Spheroidal aggregate culture of rat liver cells: histotypic reorganization biomatrix depos-ition and maintenance of functional activities. J Cell Biol 1985;101(3):914-923.
  60. Abu-Absi SF, Friend JR, Hansen LK, Hu WS. Structural polarity and functional bile canaliculi in rat hepatocyte spheroids. Exp Cell Res 2002;274 (1):56-67.
  61. Lazar A, Peshwa MV, Wu FJ, Chi CM, Cerra FB, Hu WS. Formation of porcine hepatocyte spher-oids for use in a bioartificial liver. Cell Transplant 1995;4(3):259-268.
  62. Harada K, Mitaka T, Miyamoto, Sugimoto S, Ikeda S, Takeda H, et al. Rapid formation of hepatic organoid in collagen sponge by rat small hepatocytes and hepatic nonparenchymal cells. J Hepato 2003;39(5):716-723.
  63. Lu HF, Chua KN, Zhang PC, Lim WC, Rama-krishna S, Leong KW, et al. Three-dimensional co-culture of rat hepatocyte spheroids and NIH/3T3 fibroblasts enhances hepatocyte functional main-tenance. Acta Biomater 2005;1(4):399-410.
  64. Brieva TA, Moghe PV. Functional engineering of hepatocytes via heterocellular presentation of a homoadhesive molecule E-cadherin. Biotechnol Bioeng 2001;76(4):295-302.
  65. Sugimoto S, Mitaka T, Ikeda S, Harada K, Ikai I, Yamaoka Y, et al. Morphological changes induced by extracellular matrix are correlated with matur-ation of rat small hepatocytes. J Cell Biochem 2002;87(1):16-28.
  66. Kamiya A, Kojima N, Kinoshita T, Sakai Y, Miya-ijma A. Maturation of fetal hepatocytes in vitro by extracellular matrices and oncostatin M: induction of tryptophan oxygenase. Hepatology 2002;35(6): 1351-1359.
  67. Runge D, Runge DM, Bowen WC, Locker J, Michalopoulos GK. Matrix induced re-differenti-ation of cultured rat hepatocytes and changes of CCAAT/enhancer binding proteins. Biol Chem 1997;378(8):873-881.
  68. Kocarek TA, Schuetz EG, Guzelian PS. Expres-sion of multiple forms of cytochrome P450 mRNAs in primary cultures of rat hepatocytes maintained on matrigel. Mol Pharmacol 1993;43 (3):328-334.
  69. Ouchi H, Otsu K, Kuzumaki T, Iuchi Y, Ishikawa K. Synergistic induction by collagen and fibro-nectin of liver-specific genes in rat primary cul-tured hepatocytes. Arch Biochim Biophys 1998; 358(1):58-62.
  70. Shu SN, Wei L, Wang JH, Zhan YT, Chen HS, Wang Y. Hepatic differentiation capability of rat bone marrow-derived mesenchymal stem cells and hematopoietic stem cells. World J Gastroenterol 2004;10(19):2818-2822.
  71. Shi XL, Qiu YD, Li Q, Xie T, Zhu ZH, Chen LL, et al. Hepatocyte like cells from directed dif-ferentiation of mouse bone marrow cells in vitro. Acta Pharmacol Sin 2005;26(4):469-476.
  72. Lee J, Cuddihy MJ, Cater GM, A Kotov NA. Engineering liver tissue spheroids with inverted colloidal crystal scaffolds. Biomaterials 2009;30 (27):4687-4694.
  73. Wang W, Itaka K, Ohba S, Nishiyama N, Chung U, Yamasaki Y, et al. 3D spheroid culture system on micropatterned substrates for improved dif-ferentiation efficiency of multipotent mesen-chymal stem cells. Biomaterials 2009;30(14): 2705-2715.
  74. Chua K, Lim WS, Zhang P, Lu H, Wen J, Ramakrishna s, et al. Stable immobilization of rat hepatocyte spheroids on galactosylated nanofiber scaffold. Biomaterials 2005;26(15):2537-2547.
  75. Zavana B, Bruna P, Vindignib V, Amadoric A, Habelerc W, Pontissod P, et al. Extracellular matrix-enriched polymeric scaffolds as a substrate for hepatocyte cultures: in vitro and in vivo studies. Biomaterials 2005;26(34):7038-7045.
  76. Jiang J, Kojima N, Kinoshita T, Miyajima A, Yan W, Sakai Y. Cultivation of fetal liver cells in a three-dimensional Poly-L-lactic acid scaffold in the presence of oncostatin M. Cell. Transplant 2002;11(5):403-406.
  77. Semino CE, Merok JR, Crano GG, Panagiotakeos G, Zhang S. Functional differentiation of hepato-cyte-like spheroid structures from putative liver progenitor cells in three-dimensional peptide scaffolds. Differentiation 2003;71(4-5):262-270.
  78. Pollok JM, Kluth D, Cusick RA, Lee H, Utsuno-miya H, Ma PX, et al. Formation of spheroidal aggregates of hepatocytes on biodegradable poly-mers under continuous-flow bioreactor conditions. Eur J Pediatr Surg 1998;8(4):195-199.
  79. Glicklis R, Shapiro L, Agbaria R, Merchuk JC, Cohen S. Hepatocyte behavior within three dimen-sional porous alginate scaffolds. Biotechnol Bio-eng 2000;67(3):344-353.
  80. Hashemi S, Soleimani M, Zargarian S, Haddadi-Asl V, Ahmadbeigi N, Soudi S, et al. In vitro dif-ferentiation of human cord blood-derived unre-stricted somatic stem cells into hepatocyte-like cells on poly ( -Caprolactone) nanofiber scaf-folds. Cells Tissues Organs 2009;190(3):135-149.
  81. Kazemnejad S, Allameh A, Soleimani M, Ghareh-baghian A, Mohammadi Y, Amirizadeh N, et al. Functional hepatocyte-like cells derived from human bone marrow mesenchymal stem cells on a novel 3-dimensional biocompatible nanofibrous scaffold. Int J Artif Organs 2008;31(6):500-507.
  82. Kazemnejad S, Allameh A, Soleimani M, Ghareh-baghian A, Mohammadi Y, Amirizadeh N, et al. Biochemical and molecular characterization of hepatocyte-like cells derived from human bone marrow mesenchymal stem cells on a novel three-dimensional biocompatible nanofibrous scaffold. J Gastroenterol Hepatol 2009;24(2):278-287.
  83. Gupta S, Malhi H, Gorla GR. Re-Engineering the liver with natural biomaterials. Yonsei Med J 2000;41(6):814-824.
  84. Ikebukuro H, Inagaki M, Mito M, Kasai S, Ogawa K, Nozawa M. Prolonged function of hepatocytes transplanted into the spleens of Nagase analbumin-emic rats. Eur Surg Res 1999:31(1);39-47.
  85. Mito M, Ebata H, Kusano M, Onishi T, Saito T, Sakamoto S. Morphology and function of isolated hepatocytes transplanted into rat spleen. Trans-plantation 1979;28(6):499-505.
  86. Mooney D, Johnson L, Cima L. Principles of tissue engineering and reconstruction using poly-mer cell constructs. Mat Res Soc Symp Proc 1992; 252:345-352.
  87. Mikos AG, Sarakinos G, Lyman MD, Ingber DE, Vacanti JP, Langer R. Prevascularization of porous biodegradable polymers. Biotechnol Bioeng 1993; 42(6):716-723.
  88. Cima LG, Ingber DE, Vacanti JP, Langer R. Hepatocyte culture on biodegradable polymeric substrates. Biotechnol Bioeng 1991;38(2):145-158.
  89. Higashiyama S, Noda M, Muraoka S, Hirose M, Ohgushi H, Kawase M, et al. Transplantation of hepatocytes cultured on hydorxyapatite into Nagase analbuminemia rats. J Biosci Bioeng 2003; 96(1):83-85.
  90. Yagi K, Sumiyoshi N, Yamada C, Michibayashi N, Nakashima Y, Kawase M, et al. In vitro main-tenance of liver function in hierarchical co-culture of hepatocytes and non-parenchymal liver cells. J Ferment Bioeng 1995;80(6):575-579.
  91. Higashiyama S, Noda M, Muraoka S, Uyama N, Kawada N, Ide T, et al. Maintenance of hepatocyte functions in co-culture of hepatic stellate cells. Biochem Eng J 2004;20(2-3):113-118.
  92. Takeda M, Yamamoto M, Katsuhiro I, Higa-shiyama S, Hirose M, Ohgushi H, et al. Availabil-ity of bone marrow stromal cells in three dimen-sional co-culture with hepatocytes and transplanta-tion into liver-damaged mice. J Biosci Bioeng 2005;100(1):77-81.
  93. Takeda T, Kim TH, Lee SK, Davis J, Vacanti JP. Hepatocyte transplantation in biodegradable polymer scaffolds using the dalmatian dog model of hyperuricosuria. Transplant Proc 1995;27(1): 635-636.
  94. Takeda T, Murphy S, Uyama S, Organ GM, Sch-loo BL, Vacanti JP. Hepatocyte transplantation in swine using prevascularized polyvinyl alcohol sponges. Tissue Eng 2007;1(3):253-262.

Home | About us | Contact us | Search | Site Map | Feeds | Rights & Permissions

"Avicenna Journal of Medical Biotechnology - A.J.M.B." is owned, published, and copyrighted by © 2021 Avicenna Research Institute. (pISSN: 2008-2835 .::. eISSN: 2008-4625)

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.

Creative Commons License