Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Hepatology International
Published in: Hepatology International 3/2012

01-06-2012 | Review Article

Model systems and clinical applications of hepatic stem cells for liver regeneration

Authors: Min Zhang, Yan Zhong, Jun Chen

Published in: Hepatology International | Issue 3/2012

Login to get access

Abstract

Background

Hepatic stem cells are capable to self-renew and to differentiate into all types of cells in the liver, including hepatic progenitors, mature hepatocytes and cholangiocytes.

Aims

This review summarizes the recent advances in animal studies and the results of clinical trials over the last few decades.

Results

Studies in numerous animal models of liver diseases have demonstrated the efficacy of hepatic stem cells. Clinical studies of hepatic stem cells are also promising for a variety of hepatic diseases.

Conclusions

With the accumulation of innovative and creative works, hepatic stem cells therapy will be a new approach for liver diseases.
Literature
1.
Lorenzini S, Andreone P. Regenerative medicine and liver injury: what role for bone marrow derived stem cells? Curr Stem Cell Res Ther 2007;2(1):83–88PubMed
2.
Schmelzer E, Zhang L, Bruce A, Wauthier E, Ludlow J, Yao HL, Moss N, Melhem A, McClelland R, Turner W, Kulik M, Sherwood S, Tallheden T, Cheng N, Furth ME, Reid LM. Human hepatic stem cells from fetal and postnatal donors. J Exp Med 2007;204(8):1973–1987PubMed
3.
Schmelzer E, Triolo F, Turner ME, Thompson RL, Zeilinger K, Reid LM, Gridelli B, Gerlach JC. Three-dimensional perfusion bioreactor culture supports differentiation of human fetal liver cells. Tissue Eng Part A 2010;16(6):2007–2016PubMed
4.
Seo MJ, Suh SY, Bae YC, Jung JS. Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo. Biochem Biophys Res Commun 2005;328(1):258–264PubMed
5.
Hamazaki T, Iiboshi Y, Oka M, Papst PJ, Meacham AM, Zon LI, Terada N. Hepatic maturation in differentiating embryonic stem cells in vitro. FEBS Lett 2001;497(1):15–19PubMed
6.
Yamamoto H, Quinn G, Asari A, Yamanokuchi H, Teratani T, Terada M, Ochiya T. Differentiation of embryonic stem cells into hepatocytes: biological functions and therapeutic application. Hepatology 2003;37(5):983–993PubMed
7.
Piscaglia AC, Novi M, Campanale M, Gasbarrini A. Stem cell-based therapy in gastroenterology and hepatology. Minim Invasive Ther Allied Technol 2008;17(2):100–118PubMed
8.
Flohr TR, Bonatti H Jr, Brayman KL, Pruett TL. The use of stem cells in liver disease. Curr Opin Organ Transpl 2009;14(1):64–71
9.
Baptista PM, Siddiqui MM, Lozier G, Rodriguez SR, Atala A, Soker S. The use of whole organ decellularization for the generation of a vascularized liver organoid. Hepatology 2011;53(2):604–617PubMed
10.
Erker L, Grompe M. Signaling networks in hepatic oval cell activation. Stem Cell Res 2007;1:90–102PubMed
11.
Okaya A, Kitanaka J, Kitanaka N, Satake M, Kim Y, Terada K, Sugiyama T, Takemura M, Fujimoto J, Terada N, Miyajima A, Tsujimura T. Oncostatin M inhibits proliferation of rat oval cells, OC15–5, inducing differentiation into hepatocytes. Am J Pathol 2005;166:709–719PubMed
12.
Fan JH, Shen H, Dai QM, Minuk GY, Burzynski FJ, Gong YW. Bone morphogenetic protein-4 induced rat hepatic progenitor cell (WB-F344 cell) differentiation toward hepatocyte lineage. J Cell Physiol 2009;220:72–81PubMed
13.
Laszlo V, Dezso K, Baghy K, Papp V, Kovalszky I, Safrany G, Thorgeirsson SS, Nagy P, Paku S. Triiodothyronine accelerates differentiation of rat liver progenitor cells into hepatocytes. Histochem Cell Biol 2008;130:1005–1014PubMed
14.
Suetsugu A, Nagaki M, Aoki H, Motohashi T, Kunisada T, Moriwaki H. Differentiation of mouse hepatic progenitor cells induced by hepatocyte nuclear factor-4 and cell transplantation in mice with liver fibrosis. Transplantation 2008;86:1178–1186PubMed
15.
Parviz F, Matullo C, Garrison WD, Savatski L, Adamson JW, Ning G, Kaestner KH, Rossi JM, Zaret KS, Duncan SA. Hepatocyte nuclear factor 4 alpha controls the development of a hepatic epithelium and liver morphogenesis. Nat Genet 2003;34:292–296PubMed
16.
Yamasaki H, Sada A, Iwata T, Niwa T, Tomizawa M, Xanthopoulos KG, Koike T, Shiojiri N. Suppression of C/EBP alpha expression in periportal hepatoblasts may stimulate biliary cell differentiation through increased Hnf6 and Hnf1b expression. Development 2006;133:4233–4243PubMed
17.
Huang P, He Z, Ji S, Sun H, Xiang D, Liu C, Hu Y, Wang X, Hui L. Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors. Nature 2011;475:386–389PubMed
18.
Sekiya S, Suzuki A. Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors. Nature 2011;475:390–393PubMed
19.
Lemaigre F, Zaret KS. Liver development update: new embryo models, cell lineage control, and morphogenesis. Curr Opin Genet Dev 2004;14(5):582–590PubMed
20.
Zaret KS, Grompe M. Generation and regeneration of cells of the liver and pancreas. Science 2008;322:1490–1494PubMed
21.
Darnell JE Jr, Kerr IM, Stark GR. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 1994;264:1415–1421PubMed
22.
Bromberg J, Darnell JE Jr. The role of STATs in transcriptional control and their impact on cellular function. Oncogene 2000;9(21):2468–2473
23.
Jackson LN, Larson SD, Silva SR, Rychahou PG, Chen LA, Qiu S, et al. PI3K/Akt activation is critical for early hepatic regeneration after partial hepatectomy. Am J Physiol Gastrointest Liver Physiol 2008;294(6):G1401–G1410PubMed
24.
Shinozuka H, Lombardi B, Sell S, Iammarino RM. Early histological and functional alterations of ethionine liver carcinogenesis in rats fed a choline-deficient diet. Cancer Res 1978;38(4):1092–1098PubMed
25.
Lemire JM, Shiojiri N, Fausto N. Oval cell proliferation and the origin of small hepatocytes in liver injury induced by d-galactosamine. Am J Pathol 1991;139(3):535–552PubMed
26.
Paku S, Schnur J, Nagy P, Thorgeirsson SS. Origin and structural evolution of the early proliferating oval cells in rat liver. Am J Pathol 2001;158(4):1313–1323PubMed
27.
Turner R, Lozoya O, Wang Y, Cardinale V, Gaudio E, Alpini G, Mendel G, Wauthier E, Barbier C, Alvaro D, Reid LM. Human hepatic stem cell and maturational liver lineage biology. Hepatology 2011;53(3):1035–1045PubMed
28.
Petersen BE, Zajac VF, Michalopoulos GK. Hepatic oval cell activation in response to injury following chemically induced periportal or pericentral damage in rats. Hepatology 1998a;27(4):1030–1038PubMed
29.
Qiu Q, Hernandez JC, Dean AM, Rao P, Darlington G. CD24 positive cells from normal adult mouse liver are hepatocyte progenitor cells. Stem Cells Dev 2011; (Epub ahead of print)
30.
Jelnes P, Santoni-Rugiu E, Rasmussen M, Friis SL, Nielsen JH, Tygstrup N, Bisgaard HC. Remarkable heterogeneity displayed by oval cells in rat and mouse models of stem cell-mediated liver regeneration. Hepatology 2007;5(6):1462–1470
31.
Kamiya A, Kakinuma S, Yamazaki Y, Nakauchi H. Enrichment and clonal culture of progenitor cells during mouse postnatal liver development in mice. Gastroenterology 2009;137(3):1114–1126PubMed
32.
Duret C, Gerbal-Chaloin S, Ramos J, Fabre JM, Jacquet E, Navarro F, Blanc P, Sa-Cunha A, Maurel P, Daujat-Chavanieu M. Isolation, characterization, and differentiation to hepatocyte-like cells of nonparenchymal epithelial cells from adult human liver. Stem Cells 2007;25(7):1779–1790PubMed
33.
Herrera MB, Bruno S, Buttiglieri S, Tetta C, Gatti S, Deregibus MC, Bussolati B, Camussi G. Isolation and characterization of a stem cell population from adult human liver. Stem Cells 2006;24(12):2840–2850PubMed
34.
Schmelzer E, Wauthier E, Reid LM. The phenotypes of pluripotent human hepatic progenitors. Stem Cells 2006;24(8):1852–1858PubMed
35.
Sakai H, Tagawa Y, Tamai M, Motoyama H, Ogawa S, Soeda J, Nakata T, Miyagawa S. Isolation and characterization of portal branch ligation-stimulated Hmga2-positive bipotent hepatic progenitor cells. Biochem Biophys Res Commun 2010;403(3–4):298–304PubMed
36.
Wang J, Clark JB, Rhee GS, Fair JH, Reid LM, Gerber DA. Proliferation and hepatic differentiation of adult-derived progenitor cells. Cells Tissues Organs 2003a;173(4):193–203
37.
Yin L, Sun M, Ilic Z, Leffert HL, Sell S. Derivation. characterization, and phenotypic variation of hepatic progenitor cell lines isolated from adult rats. Hepatology 2002a;35(2):315–324PubMed
38.
Yasui O, Miura N, Terada K, Kawarada Y, Koyama K, Sugiyama T. Isolation of oval cells from Long-Evans Cinnamon rats and their transformation into hepatocytes in vivo in the rat liver. Hepatology 1997;25(2):329–334PubMed
39.
Wang X, Foster M, Al-Dhalimy M, Lagasse E, Finegold M, Grompe M. The origin and liver repopulating capacity of murine oval cells. Proc Natl Acad Sci USA Suppl 2003b;1:11881–11888
40.
Wu CX, Zou Q, Zhu ZY, Gao YT, Wang YJ. Intrahepatic transplantation of hepatic oval cells for fulminant hepatic failure in rats. World J Gastroenterol 2009;15(12):1506–1511PubMed
41.
Li WL, Su J, Yao YC, Tao XR, Yan YB, Yu HY, Wang XM, Li JX, Yang YJ, Lau JT, Hu YP. Isolation and characterization of bipotent liver progenitor cells from adult mouse. Stem Cells 2006;24(2):322–332PubMed
42.
Shafritz DA, Oertel M. Model systems and experimental conditions that lead to effective repopulation of the liver by transplanted cells. Int J Biochem Cell Biol 2011;43(2):198–213PubMed
43.
de Lima VM, Oliveira CP, Alves VA, Chammas MC, Oliveira EP, Stefano JT, de Mello ES, Cerri GG, Carrilho FJ, Caldwell SH. A. rodent model of NASH with cirrhosis, oval cell proliferation and hepatocellular carcinoma. J Hepatol 2008;49(6):1055–1061PubMed
44.
Sell S, Leffert HL. Future therapeutic efficacy and the long-term safety in animals and even humans are anxiously awaited. J Clin Oncol 2008; 10;26(17):2800–2805
45.
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):577–605PubMed
46.
Aurich I, Mueller LP, Aurich H, Luetzkendorf J, Tisljar K, Dollinger MM, Schormann W, Walldorf J, Hengstler JG, Fleig WE, Christ B. Functional integration of hepatocytes derived from human mesenchymal stem cells into mouse livers. Gut 2007;56(3):405–415PubMed
47.
Lange C, Bassler P, Lioznov MV, Bruns H, Kluth D, Zander AR, Fiegel HC. Hepatocytic gene expression in cultured rat mesenchymal stem cells. Transpl Proc 2005;37(1):276–279
48.
Wang PP, Wang JH, Yan ZP, Hu MY, Lau GK, Fan ST, Luk JM. Expression of hepatocyte-like phenotypes in bone marrow stromal cells after HGF induction. Biochem Biophys Res Commun 2004;320(3):712–716PubMed
49.
Lee KD, Kuo TK, Whang-Peng J, Chung YF, Lin CT, Chou SH, Chen JR, Chen YP, Lee OK. In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology 2004;40(6):1275–1284PubMed
50.
Hong SH, Gang EJ, Jeong JA, Ahn C, Hwang SH, Yang IH, Park HK, Han H, Kim H. In vitro differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocyte-like cells. Biochem Biophys Res Commun 2005;330(4):1153–1161PubMed
51.
Banas A, Teratani T, Yamamoto Y, Tokuhara M, Takeshita F, Quinn G, Okochi H, Ochiya T. Adipose tissue-derived mesenchymal stem cells as a source of human hepatocytes. Hepatology 2007a;46(1):219–228PubMed
52.
Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002;418(6893):41–49PubMed
53.
Banas A, Yamamoto Y, Teratani T, Ochiya T. Stem cell plasticity: learning from hepatogenic differentiation strategies. Dev Dyn 2007b;236(12):3228–3241PubMed
54.
Banas A, Teratani T, Yamamoto Y, Tokuhara M, Takeshita F, Osaki M, Kato T, Okochi H, Ochiya T. Rapid hepatic fate specification of adipose-derived stem cells and their therapeutic potential for liver failure. J Gastroenterol Hepatol 2009;24(1):70–77PubMed
55.
Kuo TK, Hung SP, Chuang CH, Chen CT, Shih YR, Fang SC, Yang VW, Lee OK. Stem cell therapy for liver disease: parameters governing the success of using bone marrow mesenchymal stem cells. Gastroenterology 2008;134(7):2111–2123PubMed
56.
Yagi K, Kojima M, Oyagi S, Ikeda E, Hirose M, Isoda K, Kawase M, Kondoh M, Ohgushi H. Application of mesenchymal stem cells to liver regenerative medicine. Yakugaku Zasshi 2008;128(1):3–9PubMed
57.
Lam SP, Luk JM, Man K, Ng KT, Cheung CK, Rose-John S, Lo CM. Activation of interleukin-6-induced glycoprotein 130/signal transducer and activator of transcription 3 pathway in mesenchymal stem cells enhances hepatic differentiation, proliferation, and liver regeneration. Liver Transpl 2010;16(10):1195–206PubMed
58.
Bulte JW, Zhang S, van Gelderen P, Herynek V, Jordan EK, Duncan ID, Frank JA. Neurotransplantation of magnetically labeled oligodendrocyte progenitors: magnetic resonance tracking of cell migration and myelination. Proc Natl Acad Sci USA 1999;96(26):15256–15261PubMed
59.
Bulte JW, Douglas T, Witwer B, Zhang SC, Strable E, Lewis BK, Zywicke H, Miller B, van Gelderen P, Moskowitz BM, Duncan ID, Frank JA. Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells. Nat Biotechnol 2001;19(12):1141–1147PubMed
60.
Hoehn M, Kustermann E, Blunk J, Wiedermann D, Trapp T, Wecker S, Focking M, Arnold H, Hescheler J, Fleischmann BK, Schwindt W, Buhrle C. Monitoring of implanted stem cell migration in vivo: a highly resolved in vivo magnetic resonance imaging investigation of experimental stroke in rat. Proc Natl Acad Sci USA 2002;99(25):16267–16272PubMed
61.
Son KR, Chung SY, Kim HC, Kim HS, Choi SH, Lee JM, Moon WK. MRI of magnetically labeled mesenchymal stem cells in hepatic failure model. World J Gastroenterol 2010;16(44):5611–5615PubMed
62.
Bos C, Delmas Y, Desmouliere A, Solanilla A, Hauger O, Grosset C, Dubus I, Ivanovic Z, Rosenbaum J, Charbord P, Combe C, Bulte JW, Moonen CT, Ripoche J, Grenier N. In vivo MR imaging of intravascularly injected magnetically labeled mesenchymal stem cells in rat kidney and liver. Radiology 2004;233(3):781–789PubMed
63.
Ju S, Teng GJ, Lu H, Zhang Y, Zhang A, Chen F, Ni Y. In vivo MR tracking of mesenchymal stem cells in rat liver after intrasplenic transplantation. Radiology 2007;245(1):206–215PubMed
64.
Kim TH, Kim JK, Shim W, Kim SY, Park TJ, Jung JY. Tracking of transplanted mesenchymal stem cells labeled with fluorescent magnetic nanoparticle in liver cirrhosis rat model with 3-T MRI. Magn Reson Imaging 2010a;28(7):1004–1013PubMed
65.
am Esch JS 2nd, Knoefel WT, Klein M, Ghodsizad A, Fuerst G, Poll LW, Piechaczek C, Burchardt ER, Feifel N, Stoldt V, Stockschläder M, Stoecklein N, Tustas RY, Eisenberger CF, Peiper M, Häussinger D, Hosch SB.Portal application of autologous CD133+ bone marrow cells to the liver: a novel concept to support hepatic regeneration. Stem Cells 2005;23(4):463–470
66.
Saito T, Okumoto K, Haga H, Nishise Y, Ishii R, Sato C, Watanabe H, Okada A, Ikeda M, Togashi H, Ishikawa T, Terai S, Sakaida I, Kawata S. Potential therapeutic application of intravenous autologous bone marrow infusion in patients with alcoholic liver cirrhosis. Stem Cells Dev 2011; (Epub ahead of print)
67.
Kharaziha P, Hellström PM, Noorinayer B, Farzaneh F, Aghajani K, Jafari F, Telkabadi M, Atashi A, Honardoost M, Zali MR, Soleimani M. Improvement of liver function in liver cirrhosis patients after autologous mesenchymal stem cell injection: a phase I–II clinical trial. Eur J Gastroenterol Hepatol 2009;21(10):1199–1205PubMed
68.
Couto BG, Goldenberg RC, da Fonseca LM, Thomas J, Gutfilen B, Resende CM, Azevedo F, Mercante DR, Torres AL, Coelho HS, Maiolino A, Alves AL, Dias JV, Moreira MC, Sampaio AL, Sousa MA, Kasai-Brunswick TH, Souza SA, Campos-de-Carvalho AC, Rezende GF. Bone marrow mononuclear cell therapy for patients with cirrhosis: a phase 1 study. Liver Int 2011;31(3):391–400PubMed
69.
Pai M, Zacharoulis D, Milicevic MN, Helmy S, Jiao LR, Levicar N, Tait P, Scott M, Marley SB, Jestice K, Glibetic M, Bansi D, Khan SA, Kyriakou D, Rountas C, Thillainayagam A, Nicholls JP, Jensen S, Apperley JF, Gordon MY, Gordon MY, Habib NA. Autologous infusion of expanded mobilized adult bone marrow-derived CD34+ cells into patients with alcoholic liver cirrhosis. Am J Gastroenterol 2008;103(8):1952–1958PubMed
70.
Kim JK, Park YN, Kim JS, Park MS, Paik YH, Seok JY, Chung YE, Kim HO, Kim KS, Ahn SH, Kim do Y, Kim MJ, Lee KS, Chon CY, Kim SJ, Terai S, Sakaida I, Han KH. Autologous bone marrow infusion activates the progenitor cell compartment in patients with advanced liver cirrhosis. Cell Transpl 2010b;19(10):1237–1246
71.
Qin AC, Liao CX, Wang Y, Yuan J, Huang YP, Lia XX, Lai YQ, Gong ZY. Intrahepatic transplantation of in vitro induced autologous bone marrow-derived liver stem cells in patients with posthepatitic cirrhosis[Article in Chinese]. Nan Fang Yi Ke Da Xue Xue Bao 2010;30(3):529–531PubMed
72.
Mohamadnejad M, Alimoghaddam K, Mohyeddin-Bonab M, Bagheri M, Bashtar M, Ghanaati H, Baharvand H, Ghavamzadeh A, Malekzadeh R. Phase 1 trial of autologous bone marrow mesenchymal stem cell transplantation in patients with decompensated liver cirrhosis. Arch Iran Med 2007a;10(4):459–466PubMed
73.
Peng L, Xie DY, Lin BL, Liu J, Zhu HP, Xie C, Zheng YB, Gao ZL. Autologous bone mesenchymal stem cell transplantation in liver failure patients caused by hepatitis B: Short-term and long-term outcomes. Hepatology 2011; (Epub ahead of print)
74.
Piscaglia AC, Campanale M, Gasbarrini A, Gasbarrini G. Stem cell-based therapies for liver diseases: state of the art and new perspectives. Stem Cells Int 2010;259461
75.
Mahieu-Caputo D, Allain JE, Branger J, Coulomb A, Delgado JP, Andreoletti M, Mainot S, Frydman R, Leboulch P, Di Santo JP, Capron F, Weber A. Repopulation of athymic mouse liver by cryopreserved early human fetal hepatoblasts. Hum Gene Ther 2004;15(12):1219–1228PubMed
76.
Oertel M, Menthena A, Dabeva MD, Shafritz DA. Cell competition leads to a high level of normal liver reconstitution by transplanted fetal liver stem/progenitor cells. Gastroenterology 2006;130(2):507–520PubMed
77.
Oertel M, Menthena A, Chen YQ, Teisner B, Jensen CH, Shafritz DA. Purification of fetal liver stem/progenitor cells containing all the repopulation potential for normal adult rat liver. Gastroenterology 2008;134(3):823–832PubMed
78.
Zheng XH, Tang XP, Chen J. Efficacy of plasma exchange combined with fetal hepacyties on viral hepatitis gravis. Hunan Yi Ke Da Xue Xue Bao 2001;26(5):437–439PubMed
79.
Habibullah CM, Syed IH, Qamar A, Taher-Uz Z. Human fetal hepatocyte transplantation in patients with fulminant hepatic failure. Transplantation 1994;58(8):951–952PubMed
80.
Fujio K, Evarts RP, Hu Z, Marsden ER, Thorgeirsson SS. Expression of stem cell factor and its receptor, c-kit, during liver regeneration from putative stem cells in adult rat. Lab Invest 1994;70(4):511–516PubMed
81.
Petersen BE, Goff JP, Greenberger JS, Michalopoulos GK. Hepatic oval cells express the hematopoietic stem cell marker Thy-1 in the rat. Hepatology 1998b;27(2):433–445PubMed
82.
Petersen BE, Grossbard B, Hatch H, Pi L, Deng J, Scott EW. Mouse A6-positive hepatic oval cells also express several hematopoietic stem cell markers. Hepatology 2003;37(3):632–640PubMed
83.
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 marrow differentiate into functional hepatocyte-like cells. J Clin Invest 2002;109(10):1291–1302PubMed
84.
Heng BC, Yu H, Yin Y, Lim SG, Cao T. Factors influencing stem cell differentiation into the hepatic lineage in vitro. J Gastroenterol Hepatol 2005;20(7):975–987PubMed
85.
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 a chemically defined (HGM) medium. J Cell Biol 1996;132(6):1133–1149PubMed
86.
Michalopoulos GK, Bowen WC, Mule K, Luo J. HGF-, EGF-, and dexamethasone-induced gene expression patterns during formation of tissue in hepatic organoid cultures. Gene Expr 2003;11(2):55–75PubMed
87.
Krause DS, Theise ND, Collector MI, Henegariu O, Hwang S, Gardner R, Neutzel S, Sharkis SJ. Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 2001;105(3):369–377PubMed
88.
Wang X, Ge S, McNamara G, Hao QL, Crooks GM, Nolta JA. Albumin-expressing hepatocyte-like cells develop in the livers of immune-deficient mice that received transplants of highly purified human hematopoietic stem cells. Blood 2003c;101(10):4201–4208PubMed
89.
Jang YY, Collector MI, Baylin SB, Diehl AM, Sharkis SJ. Hematopoietic stem cells convert into liver cells within days without fusion. Nat Cell Biol 2004;6(6):532–539PubMed
90.
Lagasse E, Connors H, Al-Dhalimy M, Reitsma M, Dohse M, Osborne L, Wang X, Finegold M, Weissman IL, Grompe M. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 2000;6(11):1229–1234PubMed
91.
Wagers AJ, Sherwood RI, Christensen JL, Weissman IL. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 2002;297(5590):2256–2259PubMed
92.
Kumar KS, Lefkowitch J, Russo MW, Hesdorffer C, Kinkhabwala M, Kapur S, Emond JC, Brown RS Jr. Successful sequential liver and stem cell transplantation for hepatic failure due to primary AL amyloidosis. Gastroenterology 2002;122(7):2026–2031PubMed
93.
Terai S, Ishikawa T, Omori K, Aoyama K, Marumoto Y, Urata Y, Yokoyama Y, Uchida K, Yamasaki T, Fujii Y, Okita K, Sakaida I. Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy. Stem Cells 2006;24(10):2292–2298PubMed
94.
Nikeghbalian S, Pournasr B, Aghdami N, Rasekhi A, Geramizadeh B, Hosseini Asl SM, Ramzi M, Kakaei F, Namiri M, Malekzadeh R, Vosough Dizaj A, Malek-Hosseini SA, Baharvand H. Autologous transplantation of bone marrow-derived mononuclear and CD133(+) cells in patients with decompensated cirrhosis. Arch Iran Med 2011;14(1):12–17PubMed
95.
Levicar N, Pai M, Habib NA, Tait P, Jiao LR, Marley SB, Davis J, Dazzi F, Smadja C, Jensen SL, Nicholls JP, Apperley JF, Gordon MY. Long-term clinical results of autologous infusion of mobilized adult bone marrow derived CD34+ cells in patients with chronic liver disease. Cell Prolif 2008;41(Suppl 1):115–125PubMed
96.
Mohamadnejad M, Namiri M, Bagheri M, Hashemi SM, Ghanaati H, Zare Mehrjardi N, Kazemi Ashtiani S, Malekzadeh R, Baharvand H. Phase 1 human trial of autologous bone marrow-hematopoietic stem cell transplantation in patients with decompensated cirrhosis. World J Gastroenterol 2007b;13(24):3359–3363PubMed
97.
Barba P, Piñana JL, Fernández-Avilés F, Perez-Simón JA, Martino R, López-Guerrero E, Valcárcel D, Rovira M, Novelli S, Campos-Varela I, López-Anglada L, Vidal X, López Corral L, Carreras E, Sierra J. Pretransplant liver function impacts on the outcome of allogeneic hematopoietic stem cell transplantation: a study of 455 patients. Biol Blood Marrow Transpl 2011; (Epub ahead of print)
98.
Salama H, Zekri AR, Zern M, Bahnassy A, Loutfy S, Shalaby S, Vigen C, Burke W, Mostafa M, Medhat E, Alfi O, Huttinger E. Autologous hematopoietic stem cell transplantation in 48 patients with end-stage chronic liver diseases. Cell Transpl 2010;19(11):1475–1486
99.
Locasciulli A, Bruno B, Alessandrino EP, Meloni G, Arcese W, Bandini G, Cassibba V, Rotoli B, Morra E, Majolino I, Alberti A, Bacigalupo A; Italian Cooperative Group for Blood and Marrow Transplantation. Hepatitis reactivation and liver failure in haemopoietic stem cell transplants for hepatitis B virus (HBV)/hepatitis C virus (HCV) positive recipients: a retrospective study by the Italian group for blood and marrow transplantation. Bone Marrow Transpl 2003;31(4):295–300
100.
Mark AL, Sun Z, Warren DS, Lonze BE, Knabel MK, Melville WG, Locke JE, Montgomery RA, Cameron AM. Stem cell mobilization is life saving in an animal model of acute liver failure. Ann Surg 2010;252(4):591–596PubMed
101.
Gaia S, Smedile A, Omede P, Olivero A, Sanavio F, Balzola F, Ottobrelli A, Abate ML, Marzano A, Rizzetto M, Tarella C. Feasibility and safety of G-CSF administration to induce bone marrow-derived cells mobilization in patients with end stage liver disease. J Hepatol 2006;45(1):13–19PubMed
102.
Yan L, Han Y, Wang JH, Han HH, Zhou XM, Liu JM, YL He, Fan DM. Therapeutic potential of peripheral blood stem cell transplantation in on cirrhotic patient caused by HBV combined with HCV. EXCLI J 2008;7:13–18
103.
Levicar N, Dimarakis I, Flores C, Tracey J, Gordon MY, Habib NA. Stem cells as a treatment for chronic liver disease and diabetes. Handb Exp Pharmacol 2007;(180):243–262
104.
Lorenzini S, Isidori A, Catani L, Gramenzi A, Talarico S, Bonifazi F, Giudice V, Conte R, Baccarani M, Bernardi M, Forbes SJ, Lemoli RM, Andreone P. Stem cell mobilization and collection in patients with liver cirrhosis. Aliment Pharmacol Ther 2008;27(10):932–939PubMed
105.
Abe K, Niwa H, Iwase K, Takiguchi M, Mori M, Abe SI, Abe K, Yamamura KI. Endoderm-specific gene expression in embryonic stem cells differentiated to embryoid bodies. Exp Cell Res 1996;229(1):27–34PubMed
106.
Jones EA, Tosh D, Wilson DI, Lindsay S, Forrester LM. Hepatic differentiation of murine embryonic stem cells. Exp Cell Res 2002;272(1):15–22PubMed
107.
Yamada T, Yoshikawa M, Kanda S, Kato Y, Nakajima Y, Ishizaka S, Tsunoda Y. In vitro differentiation of embryonic stem cells into hepatocyte-like cells identified by cellular uptake of indocyanine green. Stem Cells 2002;20(2):146–154PubMed
108.
Miyashita H, Suzuki A, Fukao K, Nakauchi H, Taniguchi H. Evidence for hepatocyte differentiation from embryonic stem cells in vitro. Cell Transpl 2002;11(5):429–434
109.
Chinzei R, Tanaka Y, Shimizu-Saito K, Hara Y, Kakinuma S, Watanabe M, Teramoto K, Arii S, Takase K, Sato C, Terada N, Teraoka H. Embryoid-body cells derived from a mouse embryonic stem cell line show differentiation into functional hepatocytes. Hepatology 2002;36(1):22–29PubMed
110.
Kuai XL, Cong XQ, Li XL, Xiao SD. Generation of hepatocytes from cultured mouse embryonic stem cells. Liver Transpl 2003;9(10):1094–1099PubMed
111.
Choi D, Oh HJ, Chang UJ, Koo SK, Jiang JX, Hwang SY, Lee JD, Yeoh GC, Shin HS, Lee JS, Oh B. In vivo differentiation of mouse embryonic stem cells into hepatocytes. Cell Transpl 2002;11(4):359–368
112.
Yin Y, Lim YK, Salto-Tellez M, Ng SC, Lin CS, Lim SK. AFP(+), ESC-derived cells engraft and differentiate into hepatocytes in vivo. Stem Cells 2002b;20(4):338–346PubMed
113.
Heo J, Factor VM, Uren T, Takahama Y, Lee JS, Major M, Feinstone SM, Thorgeirsson SS. Hepatic precursors derived from murine embryonic stem cells contribute to regeneration of injured liver. Hepatology 2006;44(6):1478–1486PubMed
114.
Li F, Liu P, Liu C, Xiang D, Deng L, Li W, Wangensteen K, Song J, Ma Y, Hui L, Wei L, Li L, Ding X, Hu Y, He Z, Wang X. Hepatoblast-like progenitor cells derived from embryonic stem cells can repopulate livers of mice. Gastroenterology 2010;139(6):2158–2169PubMed
115.
Zhang H, Liu Z, Li R, Wang D, Liu W, Li J, Yu H, Zhang F, Dou K. Transplantation of embryonic small hepatocytes induces regeneration of injured liver in adult rat. Transpl Proc 2009;41(9):3887–3892
116.
Agarwal S, Holton KL, Lanza R. Efficient differentiation of functional hepatocytes from human embryonic stem cells. Stem Cells 2008b;26:1117–1127PubMed
117.
Touboul T, Hannan NR, Corbineau S, Martinez A, Martinet C, Branchereau S, Mainot S, Strick-Marchand H, Pedersen R, Di Santo J, Weber A, Vallier L. Generation of functional hepatocytes from human embryonic stem cells under chemically defined conditions that recapitulate liver development. Hepatology 2010;51(5):1754–1765PubMed
118.
Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007;131:861–872PubMed
119.
Yu J, Vodyanik MA, Smuga Otte K, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 2007;318:1917–1920PubMed
120.
Park IH, Zhao R, West JA, et al. Reprogramming of human omatic cells to pluripotency with defined factors. Nature 2008;451:141–146PubMed
121.
Rambhatla L, Chiu CP, Kundu P, Peng Y, Carpenter MK. Generation of hepatocyte-like cells from human embryonic stem cells. Cell Transpl 2003;12(1):1–11
122.
Asgari S, Pournasr B, Salekdeh GH, Ghodsizadeh A, Ott M, Baharvand H. Induced pluripotent stem cells: a new era for hepatology. J Hepatol 2010;53(4):738–751PubMed
123.
Song Z, Cai J, Liu Y, et al. Efficient generation of hepatocyte-like cells from human induced pluripotent stem cells. Cell Res 2009;19:1233–1242PubMed
124.
Sullivan GJ, Hay DC, Park IH, Fletcher J, Hannoun Z, Payne CM, Dalgetty D, Black JR, Ross JA, Samuel K, Wang G, Daley GQ, Lee JH, Church GM, Forbes SJ, Iredale JP, Wilmut I. Generation of functional human hepatic endoderm from human induced pluripotent stem cells. Hepatology 2010;51:329–335PubMed
125.
Li HY, Chien Y, Chen YJ, Chen SF, Chang YL, Chiang CH, Jeng SY, Chang CM, Wang ML, Chen LK, Hung SI, Huo TI, Lee SD, Chiou SH. Reprogramming induced pluripotent stem cells in the absence of c-Myc for differentiation into hepatocyte-like cells. Biomaterials 2011;32:5994–6005PubMed
126.
Bhave VS, Paranjpe S, Bowen WC, Donthamsetty S, Bell AW, Khillan JS, Michalopoulos GK. Genes inducing iPS phenotype play a role in hepatocyte survival and proliferation in vitro and liver regeneration in vivo.Hepatology 2011; doi:10.​1002/​hep.​24507 (Epub ahead of print)
127.
Choi SM, Kim Y, Liu H, Chaudhari P, Ye Z, Jang YY. Liver engraftment potential of hepatic cells derived from patient-specific induced pluripotent stem cells.Cell Cycle 2011;10(15) (Epub ahead of print)
128.
Liu H, Kim Y, Sharkis S, Marchionni L, Jang YY. In vivo liver regeneration potential of human induced pluripotent stem cells from diverse origins. Sci Transl Med 2011;3:82ra39
129.
Espejel S, Roll GR, McLaughlin KJ, Lee AY, Zhang JY, Laird DJ, Okita K, Yamanaka S, Willenbring H. Induced pluripotent stem cell-derived hepatocytes have the functional and proliferative capabilities needed for liver regeneration in mice. J Clin Invest 2010;120:3120–3126PubMed
130.
Lodi D, Iannitti T, Palmieri BJ. Stem cells in clinical practice: applications and warnings. Exp Clin Cancer Res 2011;17:30–39
131.
Lo B, Parham L. Ethical issues in stem cell research. Endocr Rev 2009;30:204–213PubMed
Metadata
Title
Model systems and clinical applications of hepatic stem cells for liver regeneration
Authors
Min Zhang
Yan Zhong
Jun Chen
Publication date
01-06-2012
Publisher
Springer-Verlag
Published in
Hepatology International / Issue 3/2012
Print ISSN: 1936-0533
Electronic ISSN: 1936-0541
DOI
https://doi.org/10.1007/s12072-011-9323-6

Other articles of this Issue 3/2012

Hepatology International 3/2012 Go to the issue

Original Article

Characteristics of hepatocellular carcinoma nodules newly detected by computed tomography during arteriography and arterial portography: preliminary report of a randomized controlled trial

Review Article

Transjugular intrahepatic portosystemic shunt in the treatment of portal vein thrombosis: a critical review of literature

Guidelines

Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update

Original Article

Predictive factors for platelet count after laparoscopic splenectomy in cirrhotic patients

Original Article

Hepatocyte growth factor overexpression ameliorates liver inflammation and fibrosis in a mouse model of nonalcoholic steatohepatitis

Original Article

Host genetic variants and hepatitis B virologic features in HBeAg-negative hepatitis B carriers with long-term biochemical remission
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits