International Journal of Stem Cells

Korean Society for Stem Cell Research (한국줄기세포학회)
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Regenerative Medicine of the Bile Duct: Beyond the Myth

  • Buisson, Elina Maria (Department of Translational Medicine, Graduate School of Biomedical Science and Engineering) ;
  • Jeong, Jaemin (Department of Surgery, Hanyang University College of Medicine) ;
  • Kim, Han Joon (Department of Surgery, Hanyang University College of Medicine) ;
  • Choi, Dongho (Department of Translational Medicine, Graduate School of Biomedical Science and Engineering)
  • Received : 2018.07.17
  • Accepted : 2018.09.03
  • Published : 2019.07.31
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Abstract

Cholangiopathies are rare diseases of the bile duct with high mortality rates. The current treatment for cholangiopathies is liver transplantation, but there are significant obstacles including a shortage of donors and a high risk of complications. Currently, there is only one available medicine on the market targeting cholangiopathies, and the results have been inadequate in clinical therapy. To overcome these obstacles, many researchers have used human induced pluripotent stem cells (hPSC) as a source for cholangiocyte-like cell generation and have incorporated advances in bioprinting to create artificial bile ducts for implantation and transplantation. This has allowed the field to move dramatically forward in studies of biliary regenerative medicine. In this review, the authors provide an overview of cholangiocytes, the organogenesis of the bile duct, cholangiopathies, and the current treatment and advances that have been made that are opening new doors to the study of cholangiopathies.

Keywords

Acknowledgement

This research was supported by Grants from the Medical Research Center (NRF-2017R1A5A2015395), the Bio & Medical Technology Development Program (2018M3A9H1023910, 2018M3A9H3022412) funded by the National Research Foundation of Korea (NRF) of the Ministry of Education, Science and Technology (MEST), and the Technology Innovation Program or Industrial Strategic Technology Development Program (10063334, Vascularized 3D tissue (liver/heart, cancer chip for evaluation of drug efficacy and toxicity) funded by the Ministry of Trade, Industry, & Energy of Korea.

References

  1. Tanimizu N, Miyajima A, Mostov KE. Liver progenitor cells develop cholangiocyte-type epithelial polarity in three-dimensional culture. Mol Biol Cell 2007;18:1472-1479 https://doi.org/10.1091/mbc.e06-09-0848
  2. De Assuncao TM, Jalan-Sakrikar N, Huebert RC. Regenerative medicine and the biliary tree. Semin Liver Dis 2017;37:17-27 https://doi.org/10.1055/s-0036-1597818
  3. O'Hara SP, Tabibian JH, Splinter PL, LaRusso NF. The dynamic biliary epithelia: molecules, pathways, and disease. J Hepatol 2013;58:575-582 https://doi.org/10.1016/j.jhep.2012.10.011
  4. Cervantes-Alvarez E, Wang Y, Collin de l'Hortet A, Guzman-Lepe J, Zhu J, Takeishi K. Current strategies to generate mature human induced pluripotent stem cells derived cholangiocytes and future applications. Organogenesis 2017;13:1-15 https://doi.org/10.1080/15476278.2016.1278133
  5. Tremblay KD, Zaret KS. Distinct populations of endoderm cells converge to generate the embryonic liver bud and ventral foregut tissues. Dev Biol 2005;280:87-99 https://doi.org/10.1016/j.ydbio.2005.01.003
  6. Tabibian JH, Masyuk AI, Masyuk TV, O'Hara SP, LaRusso NF. Physiology of cholangiocytes. Compr Physiol 2013;3: 541-565
  7. Strazzabosco M, Fabris L. Development of the bile ducts: essentials for the clinical hepatologist. J Hepatol 2012;56: 1159-1170 https://doi.org/10.1016/j.jhep.2011.09.022
  8. Geisler F, Nagl F, Mazur PK, Lee M, Zimber-Strobl U, Strobl LJ, Radtke F, Schmid RM, Siveke JT. Liver-specific inactivation of Notch2, but not Notch1, compromises intrahepatic bile duct development in mice. Hepatology 2008;48: 607-616 https://doi.org/10.1002/hep.22381
  9. Cardinale V, Wang Y, Carpino G, Mendel G, Alpini G, Gaudio E, Reid LM, Alvaro D. The biliary tree--a reservoir of multipotent stem cells. Nat Rev Gastroenterol Hepatol 2012;9:231-240 https://doi.org/10.1038/nrgastro.2012.23
  10. Shin S, Walton G, Aoki R, Brondell K, Schug J, Fox A, Smirnova O, Dorrell C, Erker L, Chu AS, Wells RG, Grompe M, Greenbaum LE, Kaestner KH. Foxl1-Cre-marked adult hepatic progenitors have clonogenic and bilineage differentiation potential. Genes Dev 2011;25: 1185-1192 https://doi.org/10.1101/gad.2027811
  11. Margagliotti S, Clotman F, Pierreux CE, Beaudry JB, Jacquemin P, Rousseau GG, Lemaigre FP. The Onecut transcription factors HNF-6/OC-1 and OC-2 regulate early liver expansion by controlling hepatoblast migration. Dev Biol 2007;311:579-589 https://doi.org/10.1016/j.ydbio.2007.09.013
  12. Tanimizu N, Miyajima A. Notch signaling controls hepatoblast differentiation by altering the expression of liver-enriched transcription factors. J Cell Sci 2004;117:3165-3174 https://doi.org/10.1242/jcs.01169
  13. Tchorz JS, Kinter J, Muller M, Tornillo L, Heim MH, Bettler B. Notch2 signaling promotes biliary epithelial cell fate specification and tubulogenesis during bile duct development in mice. Hepatology 2009;50:871-879 https://doi.org/10.1002/hep.23048
  14. Zong Y, Panikkar A, Xu J, Antoniou A, Raynaud P, Lemaigre F, Stanger BZ. Notch signaling controls liver development by regulating biliary differentiation. Development 2009;136:1727-1739 https://doi.org/10.1242/dev.029140
  15. Raynaud P, Carpentier R, Antoniou A, Lemaigre FP. Biliary differentiation and bile duct morphogenesis in development and disease. Int J Biochem Cell Biol 2011;43: 245-256 https://doi.org/10.1016/j.biocel.2009.07.020
  16. Hussain SZ, Sneddon T, Tan X, Micsenyi A, Michalopoulos GK, Monga SP. Wnt impacts growth and differentiation in ex vivo liver development. Exp Cell Res 2004;292:157-169 https://doi.org/10.1016/j.yexcr.2003.08.020
  17. Zong Y, Stanger BZ. Molecular mechanisms of liver and bile duct development. Wiley Interdiscip Rev Dev Biol 2012;1:643-655 https://doi.org/10.1002/wdev.47
  18. Lazaridis KN, LaRusso NF. The Cholangiopathies. Mayo Clin Proc 2015;90:791-800 https://doi.org/10.1016/j.mayocp.2015.03.017
  19. McDaniell R, Warthen DM, Sanchez-Lara PA, Pai A, Krantz ID, Piccoli DA, Spinner NB. NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway. Am J Hum Genet 2006;79:169-173 https://doi.org/10.1086/505332
  20. Kim J, Yang B, Paik N, Choe YH, and Paik YH. A case of Alagille syndrome presenting with chronic cholestasis in an adult. Clin Mol Hepatol 2017;23:260-264 https://doi.org/10.3350/cmh.2016.0057
  21. Choe JY, Kim H. Intrahepatic cholangiocarcinoma with predominant ductal plate malformation pattern. Clin Mol Hepatol 2014;20:214-217 https://doi.org/10.3350/cmh.2014.20.2.214
  22. Rizvi S, Gores GJ. Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology 2013;145: 1215-1229 https://doi.org/10.1053/j.gastro.2013.10.013
  23. Kim KA, Jeong SH. The diagnosis and treatment of primary biliary cirrhosis. Korean J Hepatol 2011;17:173-179 https://doi.org/10.3350/kjhep.2011.17.3.173
  24. Verkade HJ, Bezerra JA, Davenport M, Schreiber RA, Mieli-Vergani G, Hulscher JB, Sokol RJ, Kelly DA, Ure B, Whitington PF, Samyn M, Petersen C. Biliary atresia and other cholestatic childhood diseases: advances and future challenges. J Hepatol 2016;65:631-642 https://doi.org/10.1016/j.jhep.2016.04.032
  25. Lazaridis KN, Strazzabosco M, Larusso NF. The cholangiopathies: disorders of biliary epithelia. Gastroenterology 2004;127:1565-1577 https://doi.org/10.1053/j.gastro.2004.08.006
  26. Halilbasic E, Fuchs C, Hofer H, Paumgartner G, Trauner M. Therapy of primary sclerosing cholangitis--today and tomorrow. Dig Dis 2015;33 Suppl 2:149-163 https://doi.org/10.1159/000440827
  27. Mousa HS, Carbone M, Malinverno F, Ronca V, Gershwin ME, Invernizzi P. Novel therapeutics for primary biliary cholangitis: toward a disease-stage-based approach. Autoimmun Rev 2016;15:870-876 https://doi.org/10.1016/j.autrev.2016.07.003
  28. Merino-Azpitarte M, Lozano E, Perugorria MJ, Esparza-Baquer A, Erice O, Santos-Laso A, O'Rourke CJ, Andersen JB, Jimenez-Aguero R, Lacasta A, D'Amato M, Briz O, Jalan-Sakrikar N, Huebert RC, Thelen KM, Gradilone SA, Aransay AM, Lavin JL, Fernandez-Barrena MG, Matheu A, Marzioni M, Gores GJ, Bujanda L, Marin JJG, Banales JM. SOX17 regulates cholangiocyte differentiation and acts as a tumor suppressor in cholangiocarcinoma. J Hepatol 2017; 67:72-83 https://doi.org/10.1016/j.jhep.2017.02.017
  29. Sampaziotis F, de Brito MC, Madrigal P, Bertero A, Saeb-Parsy K, Soares FAC, Schrumpf E, Melum E, Karlsen TH, Bradley JA, Gelson WT, Davies S, Baker A, Kaser A, Alexander GJ, Hannan NRF, Vallier L. Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation. Nat Biotechnol 2015;33: 845-852 https://doi.org/10.1038/nbt.3275
  30. Sampaziotis F, Justin AW, Tysoe OC, Sawiak S, Godfrey EM, Upponi SS, Gieseck RL 3rd, de Brito MC, Berntsen NL, Gomez-Vazquez MJ, Ortmann D, Yiangou L, Ross A, Bargehr J, Bertero A, Zonneveld MCF, Pedersen MT, Pawlowski M, Valestrand L, Madrigal P, Georgakopoulos N, Pirmadjid N, Skeldon GM, Casey J, Shu W, Materek PM, Snijders KE, Brown SE, Rimland CA, Simonic I, Davies SE, Jensen KB, Zilbauer M, Gelson WTH, Alexander GJ, Sinha S, Hannan NRF, Wynn TA, Karlsen TH, Melum E, Markaki AE, Saeb-Parsy K, Vallier L. Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids. Nat Med 2017;23:954-963 https://doi.org/10.1038/nm.4360
  31. Dianat N, Dubois-Pot-Schneider H, Steichen C, Desterke C, Leclerc P, Raveux A, Combettes L, Weber A, Corlu A, Dubart-Kupperschmitt A. Generation of functional cholangiocyte-like cells from human pluripotent stem cells and HepaRG cells. Hepatology 2014;60:700-714 https://doi.org/10.1002/hep.27165
  32. Ogawa M, Ogawa S, Bear CE, Ahmadi S, Chin S, Li B, Grompe M, Keller G, Kamath BM, Ghanekar A. Directed differentiation of cholangiocytes from human pluripotent stem cells. Nat Biotechnol 2015;33:853-861 https://doi.org/10.1038/nbt.3294
  33. De Assuncao TM, Sun Y, Jalan-Sakrikar N, Drinane MC, Huang BQ, Li Y, Davila JI, Wang R, O'Hara SP, Lomberk GA, Urrutia RA, Ikeda Y, Huebert RC. Development and characterization of human-induced pluripotent stem cell-derived cholangiocytes. Lab Invest 2015;95:1218 https://doi.org/10.1038/labinvest.2015.99
  34. Kido T, Koui Y, Suzuki K, Kobayashi A, Miura Y, Chern EY, Tanaka M, Miyajima A. CPM Is a useful cell surface marker to isolate expandable bi-potential liver progenitor cells derived from human iPS cells. Stem Cell Reports 2015;5:508-515 https://doi.org/10.1016/j.stemcr.2015.08.008
  35. Aikawa M, Miyazawa M, Okamoto K, Toshimitsu Y, Torii T, Okada K, Akimoto N, Ohtani Y, Koyama I, Yoshito I. A novel treatment for bile duct injury with a tissue-engineered bioabsorbable polymer patch. Surgery 2010;147: 575-580 https://doi.org/10.1016/j.surg.2009.10.049
  36. Perez Alonso AJ, Del Olmo Rivas C, Romero IM, Canizares Garcia FJ, Poyatos PT. Tissue-engineering repair of extrahepatic bile ducts. J Surg Res 2013;179:18-21 https://doi.org/10.1016/j.jss.2012.08.035
  37. Miyazawa M, Torii T, Toshimitsu Y, Okada K, Koyama I, Ikada Y. A tissue-engineered artificial bile duct grown to resemble the native bile duct. Am J Transplant 2005;5: 1541-1547 https://doi.org/10.1111/j.1600-6143.2005.00845.x
  38. Park SH, Kang BK, Lee JE, Chun SW, Jang K, Kim YH, Jeong MA, Kim Y, Kang K, Lee NK, Choi D, Kim HJ. Design and fabrication of a thin-walled free-form scaffold on the basis of medical image data and a 3D printed template: its potential use in bile duct regeneration. Acs Appl Mater Interfaces 2017;9:12290-12298 https://doi.org/10.1021/acsami.7b00849

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