Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
December-2017 Volume 40 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December-2017 Volume 40 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Hepatic differentiation of human iPSCs in different 3D models: A comparative study

  • Authors:
    • Florian Meier
    • Nora Freyer
    • Joanna Brzeszczynska
    • Fanny Knöspel
    • Lyle Armstrong
    • Majlinda Lako
    • Selina Greuel
    • Georg Damm
    • Eva Ludwig-Schwellinger
    • Ulrich Deschl
    • James A. Ross
    • Mario Beilmann
    • Katrin Zeilinger
  • View Affiliations / Copyright

    Affiliations: Boehringer Ingelheim Pharma GmbH and Co.KG, Nonclinical Drug Safety Germany, D-88397 Biberach an der Riss, Germany, Bioreactor Group, Berlin Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, D-13353 Berlin, Germany, Tissue Injury and Repair Group, Chancellor's Building, Edinburgh Medical School, University of Edinburgh, EH164SB Edinburgh, UK, Institute of Genetic Medicine, University of Newcastle upon Tyne, NE13BZ Newcastle upon Tyne, UK, Department of Hepatobiliary Surgery and Visceral Transplantation, University of Leipzig, D-04103 Leipzig, Germany, Boehringer Ingelheim Pharma GmbH and Co.KG, Drug Metabolism and Pharmacokinetics Germany, D-88397 Biberach an der Riss, Germany
    Copyright: © Meier et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1759-1771
    |
    Published online on: October 16, 2017
       https://doi.org/10.3892/ijmm.2017.3190
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Human induced pluripotent stem cells (hiPSCs) are a promising source from which to derive distinct somatic cell types for in vitro or clinical use. Existent protocols for hepatic differentiation of hiPSCs are primarily based on 2D cultivation of the cells. In the present study, the authors investigated the generation of hiPSC-derived hepatocyte-like cells using two different 3D culture systems: A 3D scaffold-free microspheroid culture system and a 3D hollow-fiber perfusion bioreactor. The differentiation outcome in these 3D systems was compared with that in conventional 2D cultures, using primary human hepatocytes as a control. The evaluation was made based on specific mRNA expression, protein secretion, antigen expression and metabolic activity. The expression of α-fetoprotein was lower, while cytochrome P450 1A2 or 3A4 activities were higher in the 3D culture systems as compared with the 2D differentiation system. Cells differentiated in the 3D bioreactor showed an increased expression of albumin and hepatocyte nuclear factor 4α, as well as secretion of α-1-antitrypsin as compared with the 2D differentiation system, suggesting a higher degree of maturation. In contrast, the 3D scaffold-free microspheroid culture provides an easy and robust method to generate spheroids of a defined size for screening applications, while the bioreactor culture model provides an instrument for complex investigations under physiological-like conditions. In conclusion, the present study introduces two 3D culture systems for stem cell derived hepatic differentiation each demonstrating advantages for individual applications as well as benefits in comparison with 2D cultures.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

View References

1 

Lauschke VM and Ingelman-Sundberg M: The importance of patient-specific factors for hepatic drug response and toxicity. Int J Mol Sci. 17:17142016. View Article : Google Scholar :

2 

Mueller SO, Guillouzo A, Hewitt PG and Richert L: Drug biokinetic and toxicity assessments in rat and human primary hepatocytes and HepaRG cells within the EU-funded Predict-IV project. Toxicol In Vitro. 30:19–26. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Takahashi K and Yamanaka S: Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 126:663–676. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K and Yamanaka S: Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 131:861–872. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Rashid ST, Corbineau S, Hannan N, Marciniak SJ, Miranda E, Alexander G, Huang-Doran I, Griffin J, Ahrlund-Richter L, Skepper J, et al: Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells. J Clin Invest. 120:3127–3136. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Tafaleng EN, Chakraborty S, Han B, Hale P, Wu W, Soto-Gutierrez A, Feghali-Bostwick CA, Wilson AA, Kotton DN, Nagaya M, et al: Induced pluripotent stem cells model personalized variations in liver disease resulting from α1-antitrypsin deficiency. Hepatology. 62:147–157. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Si-Tayeb K, Lemaigre FP and Duncan SA: Organogenesis and development of the liver. Dev Cell. 18:175–189. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Hay DC, Fletcher J, Payne C, Terrace JD, Gallagher RC, Snoeys J, Black JR, Wojtacha D, Samuel K, Hannoun Z, et al: Highly efficient differentiation of hESCs to functional hepatic endoderm requires ActivinA and Wnt3a signaling. Proc Natl Acad Sci USA. 105:12301–12306. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Hannan NRF, Segeritz CP, Touboul T and Vallier L: Production of hepatocyte-like cells from human pluripotent stem cells. Nat Protoc. 8:430–437. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Czysz K, Minger S and Thomas N: DMSO efficiently down regulates pluripotency genes in human embryonic stem cells during definitive endoderm derivation and increases the proficiency of hepatic differentiation. PLoS One. 10:e01176892015. View Article : Google Scholar : PubMed/NCBI

11 

Szkolnicka D, Farnworth SL, Lucendo-Villarin B and Hay DC: Deriving functional hepatocytes from pluripotent stem cells. Curr Protoc Stem Cell Biol. 30:1G.5.1–12. 2014. View Article : Google Scholar

12 

Tasnim F, Phan D, Toh YC and Yu H: Cost-effective differentiation of hepatocyte-like cells from human pluripotent stem cells using small molecules. Biomaterials. 70:115–125. 2015. View Article : Google Scholar : PubMed/NCBI

13 

Schwartz RE, Trehan K, Andrus L, Sheahan TP, Ploss A, Duncan SA, Rice CM and Bhatia SN: Modeling hepatitis C virus infection using human induced pluripotent stem cells. Proc Natl Acad Sci USA. 109:2544–2548. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Bukong TN, Lo T, Szabo G and Dolganiuc A: Novel developmental biology-based protocol of embryonic stem cell differentiation to morphologically sound and functional yet immature hepatocytes. Liver Int. 32:732–741. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Siller R, Greenhough S, Naumovska E and Sullivan GJ: Small-molecule-driven hepatocyte differentiation of human pluripotent stem cells. Stem Cell Reports. 4:939–952. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Asplund A, Pradip A, van Giezen M, Aspegren A, Choukair H, Rehnström M, Jacobsson S, Ghosheh N, El Hajjam D, Holmgren S, et al: One standardized differentiation procedure robustly generates homogenous hepatocyte cultures displaying metabolic diversity from a large panel of human pluripotent stem cells. Stem Cell Rev. 12:90–104. 2016. View Article : Google Scholar

17 

Kim JH, Jang YJ, An SY, Son J, Lee J, Lee G, Park JY, Park HJ, Hwang DY, Kim JH, et al: Enhanced metabolizing activity of human ES cell-derived hepatocytes using a 3D culture system with repeated exposures to xenobiotics. Toxicol Sci. 147:190–206. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Park H-J, Choi Y-J, Kim JW, Chun HS, Im I, Yoon S, Han YM, Song CW and Kim H: Differences in the epigenetic regulation of cytochrome P450 genes between human embryonic stem cell-derived hepatocytes and primary hepatocytes. PLoS One. 10:e01329922015. View Article : Google Scholar : PubMed/NCBI

19 

Baxter M, Withey S, Harrison S, Segeritz CP, Zhang F, Atkinson-Dell R, Rowe C, Gerrard DT, Sison-Young R, Jenkins R, et al: Phenotypic and functional analyses show stem cell-derived hepatocyte-like cells better mimic fetal rather than adult hepatocytes. J Hepatol. 62:581–589. 2015. View Article : Google Scholar :

20 

Godoy P, Schmidt-Heck W, Natarajan K, Lucendo-Villarin B, Szkolnicka D, Asplund A, Björquist P, Widera A, Stöber R, Campos G, et al: Gene networks and transcription factor motifs defining the differentiation of stem cells into hepatocyte-like cells. J Hepatol. 63:934–942. 2015. View Article : Google Scholar : PubMed/NCBI

21 

Kondo Y, Iwao T, Nakamura K, Sasaki T, Takahashi S, Kamada N, Matsubara T, Gonzalez FJ, Akutsu H, Miyagawa Y, et al: An efficient method for differentiation of human induced pluripotent stem cells into hepatocyte-like cells retaining drug metabolizing activity. Drug Metab Pharmacokinet. 29:237–243. 2014. View Article : Google Scholar

22 

Cameron K, Tan R, Schmidt-Heck W, Campos G, Lyall MJ, Wang Y, Lucendo-Villarin B, Szkolnicka D, Bates N, Kimber SJ, et al: Recombinant laminins drive the differentiation and self-organization of hESC-derived hepatocytes. Stem Cell Reports. 5:1250–1262. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Takayama K, Inamura M, Kawabata K, Katayama K, Higuchi M, Tashiro K, Nonaka A, Sakurai F, Hayakawa T, Furue MK, et al: Efficient generation of functional hepatocytes from human embryonic stem cells and induced pluripotent stem cells by HNF4alpha transduction. Mol Ther. 20:127–137. 2012. View Article : Google Scholar

24 

Watanabe H, Takayama K, Inamura M, Tachibana M, Mimura N, Katayama K, Tashiro K, Nagamoto Y, Sakurai F, Kawabata K, et al: HHEX promotes hepatic-lineage specification through the negative regulation of eomesodermin. PLoS One. 9:e907912014. View Article : Google Scholar : PubMed/NCBI

25 

Tomizawa M, Shinozaki F, Motoyoshi Y, Sugiyama T, Yamamoto S and Ishige N: Transcription factors and medium suitable for initiating the differentiation of human induced pluripotent stem cells to the hepatocyte lineage. J Cell Biochem. 117:2001–2009. 2016. View Article : Google Scholar : PubMed/NCBI

26 

Vinken M, Papeleu P, Snykers S, De Rop E, Henkens T, Chipman JK, Rogiers V and Vanhaecke T: Involvement of cell junctions in hepatocyte culture functionality. Crit Rev Toxicol. 36:299–318. 2006. View Article : Google Scholar : PubMed/NCBI

27 

Ramasamy TS, Yu JS, Selden C, Hodgson H and Cui W: Application of three-dimensional culture conditions to human embryonic stem cell-derived definitive endoderm cells enhances hepatocyte differentiation and functionality. Tissue Eng Part A. 19:360–367. 2013. View Article : Google Scholar

28 

Sivertsson L, Synnergren J, Jensen J, Björquist P and Ingelman-Sundberg M: Hepatic differentiation and maturation of human embryonic stem cells cultured in a perfused three-dimensional bioreactor. Stem Cells Dev. 22:581–594. 2013. View Article : Google Scholar :

29 

Gieseck RL III, Hannan NR, Bort R, Hanley NA, Drake RA, Cameron GW, Wynn TA and Vallier L: Maturation of induced pluripotent stem cell derived hepatocytes by 3D-culture. PLoS One. 9:e863722014. View Article : Google Scholar : PubMed/NCBI

30 

Takebe T, Sekine K, Enomura M, Koike H, Kimura M, Ogaeri T, Zhang RR, Ueno Y, Zheng YW, Koike N, et al: Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature. 499:481–484. 2013. View Article : Google Scholar : PubMed/NCBI

31 

Zeilinger K, Schreiter T, Darnell M, Söderdahl T, Lübberstedt M, Dillner B, Knobeloch D, Nüssler AK, Gerlach JC and Andersson TB: Scaling down of a clinical three-dimensional perfusion multicompartment hollow fiber liver bioreactor developed for extracorporeal liver support to an analytical scale device useful for hepatic pharmacological in vitro studies. Tissue Eng Part C Methods. 17:549–556. 2011. View Article : Google Scholar : PubMed/NCBI

32 

van de Bunt M, Lako M, Barrett A, Gloyn AL, Hansson M, McCarthy MI, Beer NL and Honoré C: Insights into islet development and biology through characterization of a human iPSC-derived endocrine pancreas model. Islets. 8:83–95. 2016. View Article : Google Scholar : PubMed/NCBI

33 

Friedrich J, Seidel C, Ebner R and Kunz-Schughart LA: Spheroid- based drug screen: Considerations and practical approach. Nat Protoc. 4:309–324. 2009. View Article : Google Scholar

34 

Pfeiffer E, Kegel V, Zeilinger K, Hengstler JG, Nüssler AK, Seehofer D and Damm G: Featured article: Isolation, characterization, and cultivation of human hepatocytes and non-parenchymal liver cells. Exp Biol Med (Maywood). 240:645–656. 2015. View Article : Google Scholar

35 

Brzeszczyńska J, Johns N, Schilb A, Degen S, Degen M, Langen R, Schols A, Glass DJ, Roubenoff R, Greig CA, et al: Loss of oxidative defense and potential blockade of satellite cell maturation in the skeletal muscle of patients with cancer but not in the healthy elderly. Aging (Albany NY). 8:1690–1702. 2016. View Article : Google Scholar

36 

Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A and Speleman F: Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 3:RESEARCH00342002. View Article : Google Scholar : PubMed/NCBI

37 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

38 

Liu J, Brzeszczynska J, Samuel K, Black J, Palakkan A, Anderson RA, Gallagher R and Ross JA: Efficient episomal reprogramming of blood mononuclear cells and differentiation to hepatocytes with functional drug metabolism. Exp Cell Res. 338:203–213. 2015. View Article : Google Scholar : PubMed/NCBI

39 

Freyer N, Knöspel F, Strahl N, Amini L, Schrade P, Bachmann S, Damm G, Seehofer D, Jacobs F, Monshouwer M, et al: Hepatic differentiation of human induced pluripotent stem cells in a perfused three-dimensional multicompartment bioreactor. Biores Open Access. 5:235–248. 2016. View Article : Google Scholar : PubMed/NCBI

40 

Hoffmann SA, Müller-Vieira U, Biemel K, Knobeloch D, Heydel S, Lübberstedt M, Nüssler AK, Andersson TB, Gerlach JC and Zeilinger K: Analysis of drug metabolism activities in a miniaturized liver cell bioreactor for use in pharmacological studies. Biotechnol Bioeng. 109:3172–3181. 2012. View Article : Google Scholar : PubMed/NCBI

41 

Schyschka L, Sánchez JJ, Wang Z, Burkhardt B, Müller-Vieira U, Zeilinger K, Bachmann A, Nadalin S, Damm G and Nussler AK: Hepatic 3D cultures but not 2D cultures preserve specific transporter activity for acetaminophen-induced hepatotoxicity. Arch Toxicol. 87:1581–1593. 2013. View Article : Google Scholar : PubMed/NCBI

42 

Rennert K, Steinborn S, Gröger M, Ungerböck B, Jank AM, Ehgartner J, Nietzsche S, Dinger J, Kiehntopf M, Funke H, et al: A microfluidically perfused three dimensional human liver model. Biomaterials. 71:119–131. 2015. View Article : Google Scholar : PubMed/NCBI

43 

Varum S, Rodrigues AS, Moura MB, Momcilovic O, Easley CA IV, Ramalho-Santos J, Van Houten B and Schatten G: Energy metabolism in human pluripotent stem cells and their differentiated counterparts. PLoS One. 6:e209142011. View Article : Google Scholar : PubMed/NCBI

44 

Tirona RG, Lee W, Leake BF, Lan LB, Cline CB, Lamba V, Parviz F, Duncan SA, Inoue Y, Gonzalez FJ, et al: The orphan nuclear receptor HNF4α determines PXR- and CAR-mediated xenobiotic induction of CYP3A4. Nat Med. 9:220–224. 2003. View Article : Google Scholar : PubMed/NCBI

45 

Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, Sivertsson Å, Kampf C, Sjöstedt E, Asplund A, et al: Proteomics. Tissue-based map of the human proteome. Science. 347:12604192015. View Article : Google Scholar : PubMed/NCBI

46 

Miki T, Ring A and Gerlach J: Hepatic differentiation of human embryonic stem cells is promoted by three-dimensional dynamic perfusion culture conditions. Tissue Eng Part C Methods. 17:557–568. 2011. View Article : Google Scholar : PubMed/NCBI

47 

De Assuncao TM, Sun Y, Jalan-Sakrikar N, Drinane MC, Huang BQ, Li Y, Davila JI, Wang R, O'Hara SP, Lomberk GA, et al: Development and characterization of human-induced pluripotent stem cell-derived cholangiocytes. Lab Invest. 95:684–696. 2015. View Article : Google Scholar : PubMed/NCBI

48 

Knöspel F, Jacobs F, Freyer N, Damm G, De Bondt A, van den Wyngaert I, Snoeys J, Monshouwer M, Richter M, Strahl N, et al: In vitro model for hepatotoxicity studies based on primary human hepatocyte cultivation in a perfused 3D bioreactor system. Int J Mol Sci. 17:5842016. View Article : Google Scholar : PubMed/NCBI

49 

Singh M, Berkland C and Detamore MS: Strategies and applications for incorporating physical and chemical signal gradients in tissue engineering. Tissue Eng Part B Rev. 14:341–366. 2008. View Article : Google Scholar : PubMed/NCBI

50 

Uzel SG, Amadi OC, Pearl TM, Lee RT, So PT and Kamm RD: Simultaneous or sequential orthogonal gradient formation in a 3D cell culture microfluidic platform. Small. 12:612–622. 2016. View Article : Google Scholar :

51 

Takayama K, Kawabata K, Nagamoto Y, Kishimoto K, Tashiro K, Sakurai F, Tachibana M, Kanda K, Hayakawa T, Furue MK, et al: 3D spheroid culture of hESC/hiPSC-derived hepatocyte-like cells for drug toxicity testing. Biomaterials. 34:1781–1789. 2013. View Article : Google Scholar

52 

Ginsberg G, Hattis D, Sonawane B, Russ A, Banati P, Kozlak M, Smolenski S and Goble R: Evaluation of child/adult pharmacokinetic differences from a database derived from the therapeutic drug literature. Toxicol Sci. 66:185–200. 2002. View Article : Google Scholar : PubMed/NCBI

53 

Goldring C, Antoine DJ, Bonner F, Crozier J, Denning C, Fontana RJ, Hanley NA, Hay DC, Ingelman-Sundberg M, Juhila S, et al: Stem cell-derived models to improve mechanistic understanding and prediction of human drug-induced liver injury. Hepatology. 65:710–721. 2017. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Meier F, Freyer N, Brzeszczynska J, Knöspel F, Armstrong L, Lako M, Greuel S, Damm G, Ludwig-Schwellinger E, Deschl U, Deschl U, et al: Hepatic differentiation of human iPSCs in different 3D models: A comparative study. Int J Mol Med 40: 1759-1771, 2017.
APA
Meier, F., Freyer, N., Brzeszczynska, J., Knöspel, F., Armstrong, L., Lako, M. ... Zeilinger, K. (2017). Hepatic differentiation of human iPSCs in different 3D models: A comparative study. International Journal of Molecular Medicine, 40, 1759-1771. https://doi.org/10.3892/ijmm.2017.3190
MLA
Meier, F., Freyer, N., Brzeszczynska, J., Knöspel, F., Armstrong, L., Lako, M., Greuel, S., Damm, G., Ludwig-Schwellinger, E., Deschl, U., Ross, J. A., Beilmann, M., Zeilinger, K."Hepatic differentiation of human iPSCs in different 3D models: A comparative study". International Journal of Molecular Medicine 40.6 (2017): 1759-1771.
Chicago
Meier, F., Freyer, N., Brzeszczynska, J., Knöspel, F., Armstrong, L., Lako, M., Greuel, S., Damm, G., Ludwig-Schwellinger, E., Deschl, U., Ross, J. A., Beilmann, M., Zeilinger, K."Hepatic differentiation of human iPSCs in different 3D models: A comparative study". International Journal of Molecular Medicine 40, no. 6 (2017): 1759-1771. https://doi.org/10.3892/ijmm.2017.3190
Copy and paste a formatted citation
x
Spandidos Publications style
Meier F, Freyer N, Brzeszczynska J, Knöspel F, Armstrong L, Lako M, Greuel S, Damm G, Ludwig-Schwellinger E, Deschl U, Deschl U, et al: Hepatic differentiation of human iPSCs in different 3D models: A comparative study. Int J Mol Med 40: 1759-1771, 2017.
APA
Meier, F., Freyer, N., Brzeszczynska, J., Knöspel, F., Armstrong, L., Lako, M. ... Zeilinger, K. (2017). Hepatic differentiation of human iPSCs in different 3D models: A comparative study. International Journal of Molecular Medicine, 40, 1759-1771. https://doi.org/10.3892/ijmm.2017.3190
MLA
Meier, F., Freyer, N., Brzeszczynska, J., Knöspel, F., Armstrong, L., Lako, M., Greuel, S., Damm, G., Ludwig-Schwellinger, E., Deschl, U., Ross, J. A., Beilmann, M., Zeilinger, K."Hepatic differentiation of human iPSCs in different 3D models: A comparative study". International Journal of Molecular Medicine 40.6 (2017): 1759-1771.
Chicago
Meier, F., Freyer, N., Brzeszczynska, J., Knöspel, F., Armstrong, L., Lako, M., Greuel, S., Damm, G., Ludwig-Schwellinger, E., Deschl, U., Ross, J. A., Beilmann, M., Zeilinger, K."Hepatic differentiation of human iPSCs in different 3D models: A comparative study". International Journal of Molecular Medicine 40, no. 6 (2017): 1759-1771. https://doi.org/10.3892/ijmm.2017.3190
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team