Skip to main content
Erschienen in: Pediatric Surgery International 8/2009

01.08.2009 | Review Article

Development of hepatic tissue engineering

verfasst von: Henning Cornelius Fiegel, Ulrich Kneser, Dietrich Kluth, Roman Metzger, Holger Till, Udo Rolle

Erschienen in: Pediatric Surgery International | Ausgabe 8/2009

Einloggen, um Zugang zu erhalten

Abstract

Liver transplantation is still the only treatment for end-staged liver diseases in children. However, donor organ shortage and immunosuppression are major limitations. Thus, approaches of hepatocyte transplantation are under investigation. Using cells might permit mass expansion, cryopreservation, and the ex vivo genetic modification of cells. For the development of cell-transplantation techniques, the use of three-dimensional scaffolds as carrier was shown to be advantageous. Polymeric matrices permit the formation of a neo-tissue and stimulation by the modification of the matrix surface. Another important issue is to define the right cell type for transplantation. Adult hepatocytes have a limited growth and differentiation potential. In contrast, fetal liver cells (FLC) possess an enormous growth and a bipotential differentiation potential. Thus, these cells may be very attractive as a cell resource for developing cell-based liver replacement. A third major issue in this approach is the neo-vascularization. Therefore, the transplantation in a recently developed model using a microsurgically created arterioveno-venous (AV) loop as a central vessel for the neo-tissue was used for transplantation of FLC in a fibrin-matrix. Initial results indicated that the transplantation of FLC using the AV-loop transplantation model may be promising for the development of highly vascularized in vivo tissue-engineered liver support systems.
Literatur
1.
Zurück zum Zitat Schiff L, Schiff E (eds) (1993) Diseases of the liver, 1st edn. J.B. Lippincott, Philadelphia Schiff L, Schiff E (eds) (1993) Diseases of the liver, 1st edn. J.B. Lippincott, Philadelphia
2.
Zurück zum Zitat Harper AM, Rosendale JD (1996) The UNOS OPTN waiting list and donor registry: 1988–1996. Clin Transplant 10:69–90 Harper AM, Rosendale JD (1996) The UNOS OPTN waiting list and donor registry: 1988–1996. Clin Transplant 10:69–90
6.
Zurück zum Zitat Raper SE (1995) Hepatocyte transplantation and gene therapy. Clin Transplant 9:249–254PubMed Raper SE (1995) Hepatocyte transplantation and gene therapy. Clin Transplant 9:249–254PubMed
7.
Zurück zum Zitat Smets F, Najimi M, Sokal EM (2008) Cell transplantation in the treatment of liver diseases. Pediatr Transplant 12:6–13PubMed Smets F, Najimi M, Sokal EM (2008) Cell transplantation in the treatment of liver diseases. Pediatr Transplant 12:6–13PubMed
12.
Zurück zum Zitat Kaufmann PM, Sano K, Uyama S, Schloo B, Vacanti JP (1994) Heterotopic hepatocyte transplantation using three dimensional polymers: evaluation of the stimulatory effects by portocaval shunt or islet cell cotransplantation. Transplant Proc 26:3343–3345PubMed Kaufmann PM, Sano K, Uyama S, Schloo B, Vacanti JP (1994) Heterotopic hepatocyte transplantation using three dimensional polymers: evaluation of the stimulatory effects by portocaval shunt or islet cell cotransplantation. Transplant Proc 26:3343–3345PubMed
13.
Zurück zum Zitat Fox IJ, Chowdhury JR, Kaufmann SS, Goetzen TC, Chowdhury NR, Warkentin PI, Dorko K, Sauter BV, Strom SC (1998) Treatment of the Crigler–Najjar syndrome type I with hepatocyte transplantation. N Engl J Med 338:1422–1426. doi:10.1056/NEJM199805143382004 PubMedCrossRef Fox IJ, Chowdhury JR, Kaufmann SS, Goetzen TC, Chowdhury NR, Warkentin PI, Dorko K, Sauter BV, Strom SC (1998) Treatment of the Crigler–Najjar syndrome type I with hepatocyte transplantation. N Engl J Med 338:1422–1426. doi:10.​1056/​NEJM199805143382​004 PubMedCrossRef
15.
Zurück zum Zitat Nieto JA, Escandon J, Betancor C, Ramos J, Canton C, Cuervas-Mons V (1989) Evidence that temporary complete occlusion of splenic vessels prevents massive embolization and sudden death associated with intrasplenic hepatocellular transplantation. Transplantation 47:449–450. doi:10.1097/00007890-198903000-00009 PubMedCrossRef Nieto JA, Escandon J, Betancor C, Ramos J, Canton C, Cuervas-Mons V (1989) Evidence that temporary complete occlusion of splenic vessels prevents massive embolization and sudden death associated with intrasplenic hepatocellular transplantation. Transplantation 47:449–450. doi:10.​1097/​00007890-198903000-00009 PubMedCrossRef
16.
Zurück zum Zitat Schneider A, Attaran M, Gratz KF, Bleck JS, Winkler M, Manns MP, Ott M (2003) Intraportal infusion of 99m technetium macro aggregated albumin particles and hepatocytes in rabbits: assessment of shunting and portal hemodynamic changes. Transplantation 75:296–302. doi:10.1097/01.TP.0000044454.43076.7B PubMedCrossRef Schneider A, Attaran M, Gratz KF, Bleck JS, Winkler M, Manns MP, Ott M (2003) Intraportal infusion of 99m technetium macro aggregated albumin particles and hepatocytes in rabbits: assessment of shunting and portal hemodynamic changes. Transplantation 75:296–302. doi:10.​1097/​01.​TP.​0000044454.​43076.​7B PubMedCrossRef
17.
Zurück zum Zitat Xiandong W, Ar’Rajab A, Ahren B, Andersson R, Bengmark S (1992) The effect of pancreatic islets on transplanted hepatocytes in the treatment of acute liver failure in rats. Res Exp Med (Berl) 191:429–435. doi:10.1007/BF02576698 CrossRef Xiandong W, Ar’Rajab A, Ahren B, Andersson R, Bengmark S (1992) The effect of pancreatic islets on transplanted hepatocytes in the treatment of acute liver failure in rats. Res Exp Med (Berl) 191:429–435. doi:10.​1007/​BF02576698 CrossRef
18.
Zurück zum Zitat Demetriou AA, Whiting JF, Feldman D, Levenson SM, Chowdhury NR, Moscioni AD, Kram M, Chowdhury JR (1986) Replacement of liver function in rats by transplantation of microcarrier attached hepatocytes. Science 233:1190–1192. doi:10.1126/science.2426782 PubMedCrossRef Demetriou AA, Whiting JF, Feldman D, Levenson SM, Chowdhury NR, Moscioni AD, Kram M, Chowdhury JR (1986) Replacement of liver function in rats by transplantation of microcarrier attached hepatocytes. Science 233:1190–1192. doi:10.​1126/​science.​2426782 PubMedCrossRef
19.
22.
Zurück zum Zitat Lee H, Cusick RA, Browne F, Kim TH, Ma PX, Utsunomiya H, Langer R, Vacanti JP (2002) Local delivery of basic fibroblast growth factor increases both angiogenesis and engraftment of hepatocytes in tissue-engineered polymer devices. Transplantation 73:1589–1593. doi:10.1097/00007890-200205270-00011 PubMedCrossRef Lee H, Cusick RA, Browne F, Kim TH, Ma PX, Utsunomiya H, Langer R, Vacanti JP (2002) Local delivery of basic fibroblast growth factor increases both angiogenesis and engraftment of hepatocytes in tissue-engineered polymer devices. Transplantation 73:1589–1593. doi:10.​1097/​00007890-200205270-00011 PubMedCrossRef
23.
Zurück zum Zitat Fiegel HC, Havers J, Kneser U, Smith MK, Moeller T, Kluth D, Mooney DJ, Rogiers X, Kaufmann PM (2004) Influence of flow conditions and matrix coatings on growth and differentiation of three-dimensionally cultured rat hepatocytes. Tissue Eng 10:165–174. doi:10.1089/107632704322791817 PubMedCrossRef Fiegel HC, Havers J, Kneser U, Smith MK, Moeller T, Kluth D, Mooney DJ, Rogiers X, Kaufmann PM (2004) Influence of flow conditions and matrix coatings on growth and differentiation of three-dimensionally cultured rat hepatocytes. Tissue Eng 10:165–174. doi:10.​1089/​1076327043227918​17 PubMedCrossRef
24.
Zurück zum Zitat Kneser U, Kaufmann PM, Fiegel HC et al (1999) Heterotopic hepatocyte transplantation utilizing pancreatic islet cotransplantation for hepatotrophic stimulation: morphologic and morphometric evaluation. Pediatr Surg Int 15:168–174. doi:10.1007/s003830050547 PubMedCrossRef Kneser U, Kaufmann PM, Fiegel HC et al (1999) Heterotopic hepatocyte transplantation utilizing pancreatic islet cotransplantation for hepatotrophic stimulation: morphologic and morphometric evaluation. Pediatr Surg Int 15:168–174. doi:10.​1007/​s003830050547 PubMedCrossRef
25.
Zurück zum Zitat Uyama S, Kaufmann PM, Takeda T, Vacanti JP (1993) Delivery of whole liver-equivalent hepatocyte mass using polymer devices and hepatotrophic stimulation. Transplantation 55:932–935PubMed Uyama S, Kaufmann PM, Takeda T, Vacanti JP (1993) Delivery of whole liver-equivalent hepatocyte mass using polymer devices and hepatotrophic stimulation. Transplantation 55:932–935PubMed
27.
Zurück zum Zitat Uyama S, Kaufmann PM, Kneser U, Fiegel HC et al (2001) Hepatocyte transplantation using biodegradable matrices in ascorbic acid-deficient rats: comparison with heterotopically transplanted liver grafts. Transplant 71:1226–1231. doi:10.1097/00007890-200105150-00008 CrossRef Uyama S, Kaufmann PM, Kneser U, Fiegel HC et al (2001) Hepatocyte transplantation using biodegradable matrices in ascorbic acid-deficient rats: comparison with heterotopically transplanted liver grafts. Transplant 71:1226–1231. doi:10.​1097/​00007890-200105150-00008 CrossRef
28.
Zurück zum Zitat Berthiaume F, Moghe PV, Toner M, Yarmush ML (1996) Effect of extracellular matrix topology on cell structure, function, and physiological responsiveness: hepatocytes cultured in a sandwich configuration. FASEB J 10:1471–1484PubMed Berthiaume F, Moghe PV, Toner M, Yarmush ML (1996) Effect of extracellular matrix topology on cell structure, function, and physiological responsiveness: hepatocytes cultured in a sandwich configuration. FASEB J 10:1471–1484PubMed
29.
Zurück zum Zitat Block GD, Locker J, Bowen WC, Petersen BE, Katyal S, Strom SC, Riley T, Howard TA, Michalopoulos GK (1996) Population expansion, clonal growth, and specific differentiation patterns in primary cultures of hepatocytes induced by hgf/sf, egf and tgf alpha in a chemically defined (HGM) medium. J Cell Biol 132:1133–1149. doi:10.1083/jcb.132.6.1133 PubMedCrossRef Block GD, Locker J, Bowen WC, Petersen BE, Katyal S, Strom SC, Riley T, Howard TA, Michalopoulos GK (1996) Population expansion, clonal growth, and specific differentiation patterns in primary cultures of hepatocytes induced by hgf/sf, egf and tgf alpha in a chemically defined (HGM) medium. J Cell Biol 132:1133–1149. doi:10.​1083/​jcb.​132.​6.​1133 PubMedCrossRef
31.
Zurück zum Zitat Guguen-Guillouzo C, Clément B, Baffet G, Beaumont C, Morel-Chany E, Glaise D, Guillouzo A (1983) Maintenance and reversibility of active albumin secretion by adult rat hepatocytes co-cultured with another liver epithelial cell type. Exp Cell Res 143:47–54. doi:10.1016/0014-4827(83)90107-6 PubMedCrossRef Guguen-Guillouzo C, Clément B, Baffet G, Beaumont C, Morel-Chany E, Glaise D, Guillouzo A (1983) Maintenance and reversibility of active albumin secretion by adult rat hepatocytes co-cultured with another liver epithelial cell type. Exp Cell Res 143:47–54. doi:10.​1016/​0014-4827(83)90107-6 PubMedCrossRef
32.
33.
Zurück zum Zitat Bhatia SN, Balis UJ, Yarmush ML, Toner M (1999) Effect of cell–cell interactions in preservation of cellular phenotype: cocultivation of hepatocytes and nonparenchymal cells. FASEB J 13:1883–1900PubMed Bhatia SN, Balis UJ, Yarmush ML, Toner M (1999) Effect of cell–cell interactions in preservation of cellular phenotype: cocultivation of hepatocytes and nonparenchymal cells. FASEB J 13:1883–1900PubMed
34.
Zurück zum Zitat Mizuguchi T, Hui T, Palm K, Sugiyama N, Mitaka T, Demetriou AA, Rozga J (2001) Enhanced proliferation and differentiation of rat hepatocytes cultured with bone marrow stromal cells. J Cell Physiol 189:106–119. doi:10.1002/jcp.1136 PubMedCrossRef Mizuguchi T, Hui T, Palm K, Sugiyama N, Mitaka T, Demetriou AA, Rozga J (2001) Enhanced proliferation and differentiation of rat hepatocytes cultured with bone marrow stromal cells. J Cell Physiol 189:106–119. doi:10.​1002/​jcp.​1136 PubMedCrossRef
35.
Zurück zum Zitat Rozga J, Williams F, Ro MS, Neuzil DF, Giorgio TD, Backfisch G, Moscioni AD, Hakim R, Demetriou AA (1993) Development of a bioartificial liver: properties and function of a hollow-fiber module inoculated with liver cells. Hepatology 17:258–265PubMedCrossRef Rozga J, Williams F, Ro MS, Neuzil DF, Giorgio TD, Backfisch G, Moscioni AD, Hakim R, Demetriou AA (1993) Development of a bioartificial liver: properties and function of a hollow-fiber module inoculated with liver cells. Hepatology 17:258–265PubMedCrossRef
36.
Zurück zum Zitat Suzuki A, Zheng YW, Kondo R, Kusakabe M, Takada Y, Fukao K, Nakauchi H, Taniguchi H (2000) Flow-cytometric separation and enrichment of hepatic progenitor cells in the developing mouse liver. Hepatology 32:1230–1239. doi:10.1053/jhep.2000.20349 PubMedCrossRef Suzuki A, Zheng YW, Kondo R, Kusakabe M, Takada Y, Fukao K, Nakauchi H, Taniguchi H (2000) Flow-cytometric separation and enrichment of hepatic progenitor cells in the developing mouse liver. Hepatology 32:1230–1239. doi:10.​1053/​jhep.​2000.​20349 PubMedCrossRef
37.
Zurück zum Zitat Taniguchi H, Suzuki A, Zheng Y, Kondo R, Takada Y, Fukunaga K, Seino K, Yuzawa K, Otsuka M, Fukao K, Nakauchi H (2000) Usefulness of flow-cytometric cell sorting for the enrichment of hepatic stem and progenitor cells in the liver. Transplant Proc 32:249–251. doi:10.1016/S0041-1345(99)00947-1 PubMedCrossRef Taniguchi H, Suzuki A, Zheng Y, Kondo R, Takada Y, Fukunaga K, Seino K, Yuzawa K, Otsuka M, Fukao K, Nakauchi H (2000) Usefulness of flow-cytometric cell sorting for the enrichment of hepatic stem and progenitor cells in the liver. Transplant Proc 32:249–251. doi:10.​1016/​S0041-1345(99)00947-1 PubMedCrossRef
38.
Zurück zum Zitat Suzuki A, Zheng YW, Kaneko S, Onodera M, Kukao K, Nakauchi H, Taniguchi H (2002) Clonal identification and characterization of self-renewing pluripotent stem cells in the developing liver. J Cell Biol 156:173–184. doi:10.1083/jcb.200108066 PubMedCrossRef Suzuki A, Zheng YW, Kaneko S, Onodera M, Kukao K, Nakauchi H, Taniguchi H (2002) Clonal identification and characterization of self-renewing pluripotent stem cells in the developing liver. J Cell Biol 156:173–184. doi:10.​1083/​jcb.​200108066 PubMedCrossRef
39.
Zurück zum Zitat Dabeva MD, Petkov PM, Sandhu J, Oren R, Laconi E, Hurston E, Shafritz DA (2000) Proliferation and differentiation of fetal liver epithelial progenitor cells after transplantation in the rat liver. Am J Pathol 156:2017–2031PubMed Dabeva MD, Petkov PM, Sandhu J, Oren R, Laconi E, Hurston E, Shafritz DA (2000) Proliferation and differentiation of fetal liver epithelial progenitor cells after transplantation in the rat liver. Am J Pathol 156:2017–2031PubMed
40.
Zurück zum Zitat Sandhu JS, Petkov PM, Dabeva MD, Shafritz DA (2001) Stem cell properties and repopulation of the rat liver by fetal liver epithelial progenitor cells. Am J Pathol 159:1323–1334PubMed Sandhu JS, Petkov PM, Dabeva MD, Shafritz DA (2001) Stem cell properties and repopulation of the rat liver by fetal liver epithelial progenitor cells. Am J Pathol 159:1323–1334PubMed
41.
Zurück zum Zitat Nierhoff D, Ogawa A, Oertel M, Chen YQ, Shafritz DA (2005) Purification and characterization of mouse fetal liver epithelial cells with high in vivo repopulation capacity. Hepatology 42:130–139. doi:10.1002/hep.20735 PubMedCrossRef Nierhoff D, Ogawa A, Oertel M, Chen YQ, Shafritz DA (2005) Purification and characterization of mouse fetal liver epithelial cells with high in vivo repopulation capacity. Hepatology 42:130–139. doi:10.​1002/​hep.​20735 PubMedCrossRef
42.
43.
Zurück zum Zitat Thorgeirsson SS (1996) Liver regeneration 9: hepatic stem cells in liver regeneration. FASEB J 10:1249–1256PubMed Thorgeirsson SS (1996) Liver regeneration 9: hepatic stem cells in liver regeneration. FASEB J 10:1249–1256PubMed
48.
Zurück zum Zitat Lazaro CA, Rhim JA, Yamada Y, Fausto N (1998) Generation of hepatocytes from oval cell precursors in culture. Cancer Res 58:5514–5522PubMed Lazaro CA, Rhim JA, Yamada Y, Fausto N (1998) Generation of hepatocytes from oval cell precursors in culture. Cancer Res 58:5514–5522PubMed
50.
Zurück zum Zitat Thorgeirsson SS, Evarts RP, Bisgaard HC, Fujio K, Hu Z (1993) Hepatic stem cell compartment: activation and lineage commitment. Proc Soc Exp Biol Med 204:253–260PubMed Thorgeirsson SS, Evarts RP, Bisgaard HC, Fujio K, Hu Z (1993) Hepatic stem cell compartment: activation and lineage commitment. Proc Soc Exp Biol Med 204:253–260PubMed
51.
Zurück zum Zitat Petersen BE, Zajak VF, Michalopoulos GK (1998) Hepatic oval cell activation in response to injury following chemically induced periportal or pericentral damage in rats. Hepatology 27:1030–1038. doi:10.1002/hep.510270419 PubMedCrossRef Petersen BE, Zajak VF, Michalopoulos GK (1998) Hepatic oval cell activation in response to injury following chemically induced periportal or pericentral damage in rats. Hepatology 27:1030–1038. doi:10.​1002/​hep.​510270419 PubMedCrossRef
54.
Zurück zum Zitat Oertel M, Menthena A, Chen YQ, Shafritz DA (2007) Comparison of hepatic properties and transplantation of Thy1+ and Thy1− cells isolated from embryonic day 14 rat fetal liver. Hepatology 46:1236–1245. doi:10.1002/hep.21775 PubMedCrossRef Oertel M, Menthena A, Chen YQ, Shafritz DA (2007) Comparison of hepatic properties and transplantation of Thy1+ and Thy1− cells isolated from embryonic day 14 rat fetal liver. Hepatology 46:1236–1245. doi:10.​1002/​hep.​21775 PubMedCrossRef
57.
Zurück zum Zitat Johnson LB, Aiken J, Mooney D, Schloo BL, Griffith-Cima L, Langer R, Vacanti JP (1994) The mesentery as a laminated vascular bed for hepatocyte transplantation. Cell Transplant 3:273–281PubMed Johnson LB, Aiken J, Mooney D, Schloo BL, Griffith-Cima L, Langer R, Vacanti JP (1994) The mesentery as a laminated vascular bed for hepatocyte transplantation. Cell Transplant 3:273–281PubMed
59.
Zurück zum Zitat Harley HA, Morgan T, Redeker AG, Reynolds TB, Villamil F, Weiner JF, Yellin A (1986) Results of a randomized trial of end-to-side portacaval shunt and distal splenorenal shunt in alcoholic liver disease and variceal bleeding. Gastroenterology 91:802–809PubMed Harley HA, Morgan T, Redeker AG, Reynolds TB, Villamil F, Weiner JF, Yellin A (1986) Results of a randomized trial of end-to-side portacaval shunt and distal splenorenal shunt in alcoholic liver disease and variceal bleeding. Gastroenterology 91:802–809PubMed
60.
Zurück zum Zitat Fiegel HC, Pryymachuk G, Rath S, Bleiziffer O, Beier JP, Bruns H, Kluth D, Metzger R, Horch RE, Till H, Kneser U (2008) Fetal hepatocyte transplantation in a vascularised AV-loop transplantation model in the rat. JCMM (in press). doi:10.1111/j.1582-4934.2008.00369.x Fiegel HC, Pryymachuk G, Rath S, Bleiziffer O, Beier JP, Bruns H, Kluth D, Metzger R, Horch RE, Till H, Kneser U (2008) Fetal hepatocyte transplantation in a vascularised AV-loop transplantation model in the rat. JCMM (in press). doi:10.​1111/​j.​1582-4934.​2008.​00369.​x
61.
Zurück zum Zitat Gilbert JC, Takada T, Stein JE, Langer R, Vacanti JP (1993) Cell transplantation of genetically altered cells on biodegradable polymer scaffolds in syngeneic rats. Transplantation 56:423–427PubMedCrossRef Gilbert JC, Takada T, Stein JE, Langer R, Vacanti JP (1993) Cell transplantation of genetically altered cells on biodegradable polymer scaffolds in syngeneic rats. Transplantation 56:423–427PubMedCrossRef
Metadaten
Titel
Development of hepatic tissue engineering
verfasst von
Henning Cornelius Fiegel
Ulrich Kneser
Dietrich Kluth
Roman Metzger
Holger Till
Udo Rolle
Publikationsdatum
01.08.2009
Verlag
Springer-Verlag
Erschienen in
Pediatric Surgery International / Ausgabe 8/2009
Print ISSN: 0179-0358
Elektronische ISSN: 1437-9813
DOI
https://doi.org/10.1007/s00383-009-2389-8

Weitere Artikel der Ausgabe 8/2009

Pediatric Surgery International 8/2009 Zur Ausgabe

Update Pädiatrie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.