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From Human-Induced Pluripotent Stem Cells to Liver Disease Modeling: A Focus on Dyslipidemia

  • Development (Section Editor: Donghun Shin)
  • Published:
Current Pathobiology Reports

Abstract

Since the reprogramming of human somatic cells into induced pluripotent stem cells (hiPSCs) became a reality, numerous advances have been made for the reprogramming process itself, cell differentiation and disease modeling. While differentiation procedures of hiPSCs into hepatocyte-like cells are under continuous investigations in order to generate fully mature and functional hepatocytes, current models already showed great promises in terms of modeling liver pathologies including metabolic diseases. This review provides an overview of the reprogramming, hepatic differentiation, and application aspects of patient-derived hepatocyte-like cells, with a more focused attention on the modeling of cholesterol metabolism defects.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676. doi:10.1016/j.cell.2006.07.024

    Article  CAS  PubMed  Google Scholar 

  2. Takahashi K, Tanabe K, Ohnuki M et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5):861–872. doi:10.1016/j.cell.2007.11.019

    Article  CAS  PubMed  Google Scholar 

  3. Yu J, Vodyanik MA, Smuga-Otto K et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318(5858):1917–1920. doi:10.1126/science.1151526

    Article  CAS  PubMed  Google Scholar 

  4. Yamanaka S (2012) Induced pluripotent stem cells: past, present, and future. Cell Stem Cell 10(6):678–684. doi:10.1016/j.stem.2012.05.005

    Article  CAS  PubMed  Google Scholar 

  5. Nordin N, Lai MI, Veerakumarasivam A, Ramasamy R (2011) Induced pluripotent stem cells : history, properties and potential applications. Med J Malaysia 66(1):4–9

    CAS  PubMed  Google Scholar 

  6. Park I-H, Zhao R, West JA et al (2008) Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451(7175):141–146. doi:10.1038/nature06534

    Article  CAS  PubMed  Google Scholar 

  7. Robinton D, Daley G (2012) The promise of induced pluripotent stem cells in research and therapy. Nature 481(7381):295–305. doi:10.1038/nature10761

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Wernig M, Meissner A, Foreman R et al (2007) In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 448(7151):318–324. doi:10.1038/nature05944

    Article  CAS  PubMed  Google Scholar 

  9. Hockemeyer D, Soldner F, Cook EG, Gao Q, Mitalipova M, Jaenisch R (2008) A drug-inducible system for direct reprogramming of human somatic cells to pluripotency. Cell Stem Cell 3(3):346–353. doi:10.1016/j.stem.2008.08.014

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Maherali N, Ahfeldt T, Rigamonti A, Utikal J, Cowan C, Hochedlinger K (2008) A high-efficiency system for the generation and study of human induced pluripotent stem cells. Cell Stem Cell 3(3):340–345. doi:10.1016/j.stem.2008.08.003

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L (2009) Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol 27(3):275–280. doi:10.1038/nbt.1529

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Dimos JT, Rodolfa KT, Niakan KK et al (2008) Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321(5893):1218–1221. doi:10.1126/science.1158799

    Article  CAS  PubMed  Google Scholar 

  13. Ebert AD, Yu J, Rose FF et al (2009) Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature 457(7227):277–280. doi:10.1038/nature07677

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Soldner F, Hockemeyer D, Beard C et al (2009) Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell 136(5):964–977. doi:10.1016/j.cell.2009.02.013

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Osakada F, Jin Z-B, Hirami Y et al (2009) In vitro differentiation of retinal cells from human pluripotent stem cells by small-molecule induction. J Cell Sci 122(Pt 17):3169–3179. doi:10.1242/jcs.050393

    Article  CAS  PubMed  Google Scholar 

  16. Choi K-D, Yu J, Smuga-Otto K et al (2009) Hematopoietic and endothelial differentiation of human induced pluripotent stem cells. Stem Cells 27(3):559–567. doi:10.1634/stemcells.2008-0922

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Ye Z, Zhan H, Mali P et al (2009) Human-induced pluripotent stem cells from blood cells of healthy donors and patients with acquired blood disorders. Blood 114(27):5473–5480. doi:10.1182/blood-2009-04-217406

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Taura D, Noguchi M, Sone M et al (2009) Adipogenic differentiation of human induced pluripotent stem cells: comparison with that of human embryonic stem cells. FEBS Lett 583(6):1029–1033. doi:10.1016/j.febslet.2009.02.031

    Article  CAS  PubMed  Google Scholar 

  19. Tanaka T, Tohyama S, Murata M et al (2009) In vitro pharmacologic testing using human induced pluripotent stem cell-derived cardiomyocytes. Biochem Biophys Res Commun. 385(4):497–502. doi:10.1016/j.bbrc.2009.05.073

    Article  CAS  PubMed  Google Scholar 

  20. Yokoo N, Baba S, Kaichi S et al (2009) The effects of cardioactive drugs on cardiomyocytes derived from human induced pluripotent stem cells. Biochem Biophys Res Commun. 387(3):482–488. doi:10.1016/j.bbrc.2009.07.052

    Article  CAS  PubMed  Google Scholar 

  21. Zhang J, Wilson GF, Soerens AG et al (2009) Functional cardiomyocytes derived from human induced pluripotent stem cells. Circ Res 104(4):e30–e41. doi:10.1161/CIRCRESAHA.108.192237

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Si-Tayeb K, Noto FK, Nagaoka M et al (2010) Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells. Hepatology 51(1):297–305. doi:10.1002/hep.23354

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Sullivan GJ, Hay DC, Park I-H et al (2010) Generation of functional human hepatic endoderm from human induced pluripotent stem cells. Hepatology 51(1):329–335. doi:10.1002/hep.23335

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Gerbal-Chaloin S, Funakoshi N, Caillaud A, Gondeau C, Champon B, Si-Tayeb K (2014) Human induced pluripotent stem cells in hepatology: beyond the proof of concept. Am J Pathol 184(2):332–347. doi:10.1016/j.ajpath.2013.09.026

    Article  PubMed  Google Scholar 

  25. • Si-Tayeb K, Lemaigre FP, Duncan SA (2010) Organogenesis and development of the liver. Dev Cell 18(2):175–189. doi:10.1016/j.devcel.2010.01.011. This paper reviews the fundamental molecular mechansims that are responsible for liver organogenesis and development which are critical to enhance our understanding and boost the technology of hiPSCs differentiation towards hepatic fate

  26. Zaret KS, Grompe M (2008) Generation and regeneration of cells of the liver and pancreas. Science 322(5907):1490–1494. doi:10.1126/science.1161431

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Lemaigre FP (2009) Mechanisms of liver development: concepts for understanding liver disorders and design of novel therapies. Gastroenterology 137(1):62–79. doi:10.1053/j.gastro.2009.03.035

    Article  CAS  PubMed  Google Scholar 

  28. D’Amour KA, Agulnick AD, Eliazer S, Kelly OG, Kroon E, Baetge EE (2005) Efficient differentiation of human embryonic stem cells to definitive endoderm. Nat Biotechnol 23(12):1534–1541. doi:10.1038/nbt1163

    Article  PubMed  Google Scholar 

  29. Song Z, Cai J, Liu Y et al (2009) Efficient generation of hepatocyte-like cells from human induced pluripotent stem cells. Cell Res 19(11):1233–1242. doi:10.1038/cr.2009.107

    Article  PubMed  Google Scholar 

  30. DeLaForest A, Nagaoka M, Si-Tayeb K et al (2011) HNF4A is essential for specification of hepatic progenitors from human pluripotent stem cells. Development 138(19):4143–4153. doi:10.1242/dev.062547

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Takayama K, Kawabata K, Nagamoto Y et al (2014) CCAAT/enhancer binding protein-mediated regulation of TGFβ receptor 2 expression determines the hepatoblast fate decision. Development 141:91–100. doi:10.1242/dev.103168

  32. Goldman O, Han S, Hamou W et al (2014) Endoderm generates endothelial cells during liver development. Stem Cell Rep 3(4):556–565. doi:10.1016/j.stemcr.2014.08.009

    Article  CAS  Google Scholar 

  33. Lorenzini S, Gitto S, Grandini E, Andreone P, Bernardi M (2008) Stem cells for end stage liver disease: how far have we got? World J Gastroenterol 14(29):4593–4599. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2738783&tool=pmcentrez&rendertype=abstract. Accessed 18 Aug 2014

  34. • Inoue H, Nagata N, Kurokawa H, Yamanaka S (2014) iPS cells: a game changer for future medicine. EMBO J 33(5):409–417. doi:10.1002/embj.201387098. This paper reviews the feasibility of using iPSCs in medicine and addresses the current demands to improve iPSCs technology for disease modeling and cell transplantation

  35. Fattahi F, Asgari S, Pournasr B et al (2013) Disease-corrected hepatocyte-like cells from familial hypercholesterolemia-induced pluripotent stem cells. Mol Biotechnol 54(3):863–873. doi:10.1007/s12033-012-9635-3

    Article  CAS  PubMed  Google Scholar 

  36. Zhang S, Chen S, Li W et al (2011) Rescue of ATP7B function in hepatocyte-like cells from Wilson’s disease induced pluripotent stem cells using gene therapy or the chaperone drug curcumin. Hum Mol Genet 20(16):3176–3187. doi:10.1093/hmg/ddr223

    Article  CAS  PubMed  Google Scholar 

  37. Yusa K, Rashid ST, Strick-Marchand H et al (2011) Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells. Nature 478(7369):391–394. doi:10.1038/nature10424

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Choi SM, Kim Y, Shim JS et al (2013) Efficient drug screening and gene correction for treating liver disease using patient-specific stem cells. Hepatology 57(6):2458–2468. doi:10.1002/hep.26237

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. •• Maetzel D, Sarkar S, Wang H et al (2014) Genetic and chemical correction of cholesterol accumulation and impaired autophagy in hepatic and neural cells derived from Niemann-Pick type C patient-specific iPS Cells. Stem cell Rep 2(6):866–880. doi:10.1016/j.stemcr.2014.03.014. This article describes the feasibility of TALENs-mediated genetic correction of a disease causing mutation in NPC patient-specific hiPSCs as a way to rescue the disease phenotypes and understand the link between the disease specific-LOF mutation and the associated phenotypes

  40. Rubin LL (2008) Stem cells and drug discovery: the beginning of a new era? Cell 132(4):549–552. doi:10.1016/j.cell.2008.02.010

    Article  CAS  PubMed  Google Scholar 

  41. Yi F, Liu G-H, Izpisua Belmonte JC (2012) Human induced pluripotent stem cells derived hepatocytes: rising promise for disease modeling, drug development and cell therapy. Protein Cell 3(4):246–250. doi:10.1007/s13238-012-2918-4

    Article  CAS  PubMed  Google Scholar 

  42. Asgari S, Pournasr B, Salekdeh GH, Ghodsizadeh A, Ott M, Baharvand H (2010) Induced pluripotent stem cells: a new era for hepatology. J Hepatol 53(4):738–751. doi:10.1016/j.jhep.2010.05.009

    Article  PubMed  Google Scholar 

  43. Szkolnicka D, Zhou W, Lucendo-Villarin B, Hay DC (2013) Pluripotent stem cell-derived hepatocytes: potential and challenges in pharmacology. Annu Rev Pharmacol Toxicol 53:147–159. doi:10.1146/annurev-pharmtox-011112-140306

    Article  CAS  PubMed  Google Scholar 

  44. Medine CN, Lucendo-Villarin B, Storck C et al (2013) Developing high-fidelity hepatotoxicity models from pluripotent stem cells. Stem Cells Transl Med 2(7):505–509. doi:10.5966/sctm.2012-0138

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Szkolnicka D, Farnworth SL, Lucendo-Villarin B, Hay DC (2014) Deriving functional hepatocytes from pluripotent stem cells. Curr Protoc Stem Cell Biol 30:1G.5.1–1G.5.12. doi:10.1002/9780470151808.sc01g05s30

    Article  Google Scholar 

  46. Yagi H, Tafaleng E, Nagaya M et al (2009) Embryonic and induced pluripotent stem cells as a model for liver disease. Crit Rev Biomed Eng 37(4–5):377–398. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3700621&tool=pmcentrez&rendertype=abstract. Accessed 9 Aug 2014

  47. Chun YS, Chaudhari P, Jang Y-Y(2010) Applications of patient-specific induced pluripotent stem cells; focused on disease modeling, drug screening and therapeutic potentials for liver disease. Int J Biol Sci 6(7):796–805. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3005346&tool=pmcentrez&rendertype=abstract

  48. Rashid ST, Corbineau S, Hannan N et al (2010) Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells. J Clin Invest. 120(9):3127–3136. doi:10.1172/JCI43122

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. •• Cayo MA, Cai J, DeLaForest A et al (2012) JD induced pluripotent stem cell-derived hepatocytes faithfully recapitulate the pathophysiology of familial hypercholesterolemia. Hepatology 56(6):2163–2171. doi:10.1002/hep.25871. This article describes the feasibility of using patient-specific hiPSCs to generate FH-hepatocytes which recapitulate key features of the disease and are competent to respond to hepatoselective pharmaceuticals thus providing a platform for the discovery of novel treatments for FH

  50. Satoh D, Maeda T, Ito T et al (2013) Establishment and directed differentiation of induced pluripotent stem cells from glycogen storage disease type Ib patient. Genes Cells 18(12):1053–1069. doi:10.1111/gtc.12101

    Article  CAS  PubMed  Google Scholar 

  51. Nakamura K, Hirano K, Wu SM (2013) iPS cell modeling of cardiometabolic diseases. J Cardiovasc Transl Res 6(1):46–53. doi:10.1007/s12265-012-9413-4

    Article  PubMed Central  PubMed  Google Scholar 

  52. Liras A (2011) Induced human pluripotent stem cells and advanced therapies: future perspectives for the treatment of haemophilia? Thromb Res 128(1):8–13. doi:10.1016/j.thromres.2011.01.010

    Article  CAS  PubMed  Google Scholar 

  53. Wu X, Robotham JM, Lee E et al (2012) Productive hepatitis C virus infection of stem cell-derived hepatocytes reveals a critical transition to viral permissiveness during differentiation. PLoS Pathog 8(4):e1002617. doi:10.1371/journal.ppat.1002617

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Yoshida T, Takayama K, Kondoh M et al (2011) Use of human hepatocyte-like cells derived from induced pluripotent stem cells as a model for hepatocytes in hepatitis C virus infection. Biochem Biophys Res Commun 416(1–2):119–124. doi:10.1016/j.bbrc.2011.11.007

    Article  CAS  PubMed  Google Scholar 

  55. Shlomai A, Schwartz RE, Ramanan V et al (2014) Modeling host interactions with hepatitis B virus using primary and induced pluripotent stem cell-derived hepatocellular systems. Proc Natl Acad Sci USA 111(33):1–6. doi:10.1073/pnas.1412631111

    Article  Google Scholar 

  56. Trapani L, Segatto M, Pallottini V (2012) Regulation and deregulation of cholesterol homeostasis: the liver as a metabolic “power station”. World J Hepatol 4(6):184–190. doi:10.4254/wjh.v4.i6.184

    Article  PubMed Central  PubMed  Google Scholar 

  57. Goldstein JL, Brown MS (2009) The LDL receptor. Arterioscler Thromb Vasc Biol 29(4):431–438. doi:10.1161/ATVBAHA.108.179564

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Faiz F, Hooper AJ, van Bockxmeer FM (2012) Molecular pathology of familial hypercholesterolemia, related dyslipidemias and therapies beyond the statins. Crit Rev Clin Lab Sci 49(1):1–17. doi:10.3109/10408363.2011.646942

    Article  CAS  PubMed  Google Scholar 

  59. Go G-W, Mani A (2012) Low-density lipoprotein receptor (LDLR) family orchestrates cholesterol homeostasis. Yale J Biol Med 85(1):19–28. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3313535&tool=pmcentrez&rendertype=abstract. Accessed 22 Aug 2014

  60. Rader DJ, Cohen J, Hobbs HH (2003) Monogenic hypercholesterolemia : new insights in pathogenesis and treatment. 111(12):1795–1803. doi:10.1172/JCI18925.Figure

    CAS  Google Scholar 

  61. Burnett JR, Ravine D, van Bockxmeer FM, Watts GF (2005) Familial hypercholesterolaemia: a look back, a look ahead. Med J Aust 182(11):552–553. http://www.ncbi.nlm.nih.gov/pubmed/15938678. Accessed 19 Aug 2014

  62. Goldstein JL, Brown MS (1974) Binding and degradation of low density lipoproteins by cultured human fibroblasts. Comparison of cells from a normal subject and from a patient with homozygous familial hypercholesterolemia. J Biol Chem 249(16):5153–5162. http://www.ncbi.nlm.nih.gov/pubmed/4368448. Accessed 23 Aug 2014

  63. Leigh SEA, Foster AH, Whittall RA, Hubbart CS, Humphries SE (2008) Update and analysis of the University College London low density lipoprotein receptor familial hypercholesterolemia database. Ann Hum Genet 72(Pt 4):485–498. doi:10.1111/j.1469-1809.2008.00436.x

    Article  CAS  PubMed  Google Scholar 

  64. Soufi M, Kurt B, Schweer H et al (2009) Genetics and kinetics of familial hypercholesterolemia, with the special focus on FH-(Marburg) p. W556R. Atheroscler Suppl 10(5):5–11. doi:10.1016/S1567-5688(09)71802-1

    Article  CAS  PubMed  Google Scholar 

  65. Seidah NG, Prat A (2007) The proprotein convertases are potential targets in the treatment of dyslipidemia. J Mol Med (Berl) 85(7):685–696. doi:10.1007/s00109-007-0172-7

    Article  CAS  Google Scholar 

  66. Abifadel M, Varret M, Rabès J-P et al (2003) Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 34(2):154–156. doi:10.1038/ng1161

    Article  CAS  PubMed  Google Scholar 

  67. Cohen JC, Boerwinkle E, Mosley TH, Hobbs HH (2006) Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 354(12):1264–1272. doi:10.1056/NEJMoa054013

    Article  CAS  PubMed  Google Scholar 

  68. Marduel M, Carrié A, Sassolas A et al (2010) Molecular spectrum of autosomal dominant hypercholesterolemia in France. Hum Mutat 31(11):E1811–E1824. doi:10.1002/humu.21348

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  69. Marques-Pinheiro A, Marduel M, Rabès J-P et al (2010) A fourth locus for autosomal dominant hypercholesterolemia maps at 16q22.1. Eur J Hum Genet 18(11):1236–1242. doi:10.1038/ejhg.2010.94

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  70. Brown M, Goldstein J (1986) A receptor-mediated pathway for cholesterol homeostasis. Science 232(4746):34–47. http://www.nobelprize.org/nobel_prizes/medicine/laureates/1985/brown-goldstein-lecture.pdf. Accessed 24 Aug 2014

  71. Sniderman AD, De Graaf J, Couture P, Williams K, Kiss RS, Watts GF (2010) Regulation of plasma LDL: the apoB paradigm. Clin Sci (Lond) 118(5):333–339. doi:10.1042/CS20090402

    Article  CAS  Google Scholar 

  72. Millar JS, Maugeais C, Ikewaki K et al (2005) Complete deficiency of the low-density lipoprotein receptor is associated with increased apolipoprotein B-100 production. Arterioscler Thromb Vasc Biol 25(3):560–565. doi:10.1161/01.ATV.0000155323.18856.a2

    Article  CAS  PubMed  Google Scholar 

  73. Rothe M, Modlich U, Schambach A (2013) Biosafety challenges for use of lentiviral vectors in gene therapy. Curr Gene Ther 13(6):453–468. http://www.ncbi.nlm.nih.gov/pubmed/24195603. Accessed 29 Aug 2014

  74. Ikonen E (2008) Cellular cholesterol trafficking and compartmentalization. Nat Rev Mol Cell Biol 9(2):125–138. doi:10.1038/nrm2336

    Article  CAS  PubMed  Google Scholar 

  75. Rosenbaum AI, Maxfield FR (2011) Niemann-Pick type C disease: molecular mechanisms and potential therapeutic approaches. J Neurochem 116(5):789–795. doi:10.1111/j.1471-4159.2010.06976.x

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  76. Schulze H, Sandhoff K (2011) Lysosomal lipid storage diseases. Cold Spring Harb Perspect Biol 3(6):a004804. doi:10.1101/cshperspect.a004804

    Article  PubMed Central  PubMed  Google Scholar 

  77. Singh R, Kaushik S, Wang Y et al (2009) Autophagy regulates lipid metabolism. Nature 458(7242):1131–1135. doi:10.1038/nature07976

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  78. Singh R, Cuervo AM (2012) Lipophagy: connecting autophagy and lipid metabolism. Int J Cell Biol 2012:282041. doi:10.1155/2012/282041

    Article  PubMed Central  PubMed  Google Scholar 

  79. Vanier MT (2010) Niemann-Pick disease type C. Orphanet J Rare Dis 5:16. doi:10.1186/1750-1172-5-16

    Article  PubMed Central  PubMed  Google Scholar 

  80. Abi-Mosleh L, Infante RE, Radhakrishnan A, Goldstein JL, Brown MS (2009) Cyclodextrin overcomes deficient lysosome-to-endoplasmic reticulum transport of cholesterol in Niemann-Pick type C cells. Proc Natl Acad Sci USA 106(46):19316–19321. doi:10.1073/pnas.0910916106

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  81. Dianat N, Steichen C, Vallier L, Weber A, Dubart-Kupperschmitt A (2013) Human pluripotent stem cells for modelling human liver diseases and cell therapy. Curr Gene Ther 13(2):120–132. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3882648&tool=pmcentrez&rendertype=abstract

  82. Savla JJ, Nelson BC, Perry CN, Adler ED (2014) Induced pluripotent stem cells for the study of cardiovascular disease. J Am Coll Cardiol 64(5):512–519. doi:10.1016/j.jacc.2014.05.038

    Article  PubMed  Google Scholar 

  83. Ding Q, Strong A, Patel KM et al (2014) Permanent alteration of PCSK9 with in vivo CRISPR-Cas9 genome editing. Circ Res 115:488–492. doi:10.1161/CIRCRESAHA.115.304351

  84. Rashid ST, Alexander GJM (2013) Induced pluripotent stem cells: from Nobel Prizes to clinical applications. J Hepatol 58(3):625–629. doi:10.1016/j.jhep.2012.10.026

    Article  PubMed  Google Scholar 

  85. Lancaster MA, Knoblich JA (2014) Organogenesis in a dish: modeling development and disease using organoid technologies. Science 345(6194):1247125. doi:10.1126/science.1247125

    Article  PubMed  Google Scholar 

  86. Takebe T, Zhang R, Koike H et al (2014) Generation of a vascularized and functional human liver from an iPSC-derived organ bud transplant. doi:10.1038/nprot.2014.020

    Google Scholar 

  87. Schwartz RE, Trehan K, Andrus L et al (2011) Modeling hepatitis C virus infection using human induced pluripotent stem cells. Proc Natl Acad Sci USA. doi:10.1073/pnas.1121400109

    Google Scholar 

  88. Leung A, Nah SK, Reid W et al (2013) Induced pluripotent stem cell modeling of multisystemic, hereditary transthyretin amyloidosis. Stem cell Rep 1(5):451–463. doi:10.1016/j.stemcr.2013.10.003

    Article  CAS  Google Scholar 

  89. Isono K, Jono H, Ohya Y et al (2014) Generation of familial amyloidotic polyneuropathy-specific induced pluripotent stem cells. Stem Cell Res. 12(2):574–583. doi:10.1016/j.scr.2014.01.004

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by grants from the VaCaRMe project funded by the Région Pays de la Loire (KST, SI, BC), the FP7 Marie Curie IRG 277188/IPSMILD (KST), the Leducq Fundation (KST, BC), the Cariplo Fundazione (BC), the Fondation Genavie (KST, BC), the Lebanese University President grant (KZ) and a scholarship from the Association of Scientific Orientation and Specialization—ASOS (SI).

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Authors and Affiliations

  1. INSERM, UMR1087-CNRS UMR6291, l’Institut du Thorax, 44000, Nantes, France

    Salam Idriss, Bertrand Cariou & Karim Si-Tayeb

  2. Faculté de Médecine, Institut du Thorax, Université de Nantes, 44000, Nantes, France

    Salam Idriss, Bertrand Cariou & Karim Si-Tayeb

  3. ER045, EDST-PRASE, Laboratory of Stem Cells, Biology Department, Faculty of Sciences, Lebanese University, Beirut, Lebanon

    Salam Idriss & Kazem Zibara

  4. Department of Endocrinology, University Hospital of Nantes, 44000, Nantes, France

    Bertrand Cariou

  5. 8 quai Moncousu, BP70721, 44007, Nantes Cedex 1, France

    Salam Idriss, Bertrand Cariou & Karim Si-Tayeb

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  1. Salam Idriss
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  2. Kazem Zibara
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Correspondence to Karim Si-Tayeb.

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Idriss, S., Zibara, K., Cariou, B. et al. From Human-Induced Pluripotent Stem Cells to Liver Disease Modeling: A Focus on Dyslipidemia. Curr Pathobiol Rep 3, 47–56 (2015). https://doi.org/10.1007/s40139-015-0067-1

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