Skip to main content

Conversion of Fibroblasts to Hepatocyte-Like Cells In Vivo

  • Protocol
  • First Online:
  • 1688 Accesses

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1905))

Abstract

In vivo conversion of fibroblasts into hepatocyte-like cells provides one potential approach for the treatment of liver fibrosis. In our previous study, we showed in vivo conversion of myofibroblasts into induced hepatocytes (iHeps) by forced expression of four transcription factors in genetic fate-tracing mouse model of chronic liver disease. These in vivo-generated iHeps showed similar expression profile with endogenous hepatocytes (eHeps) and also exhibited similar functional characteristics, such as albumin secretion, urea synthesis, cytochrome activity, and drug responsiveness. Furthermore, the targeted expression of our reprogramming factors in myofibroblasts attenuated liver fibrosis. Our study suggests that in vivo reprogramming may open new perspectives for the treatment of diseases such as liver fibrosis.

This is a preview of subscription content, log in via an institution.

Buying options

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Huang PY, He ZY, Ji SY, Sun HW, Xiang D, Liu CC, Hu YP, Wang X, Hui LJ (2011) Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors. Nature 475:386–U142

    Article  CAS  PubMed  Google Scholar 

  2. Huang P, Zhang L, Gao Y, He Z, Yao D, Wu Z, Cen J, Chen X, Liu C, Hu Y et al (2014) Direct reprogramming of human fibroblasts to functional and expandable hepatocytes. Cell Stem Cell 14:370–384

    Article  CAS  PubMed  Google Scholar 

  3. Sekiya S, Suzuki A (2011) Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors. Nature 475:390–393

    Article  CAS  Google Scholar 

  4. Yang R, Zheng Y, Li L, Liu S, Burrows M, Wei Z, Nace A, Herlyn M, Cui R, Guo W et al (2014) Direct conversion of mouse and human fibroblasts to functional melanocytes by defined factors. Nat Commun 5:5807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Song G, Pacher M, Balakrishnan A, Yuan Q, Tsay HC, Yang D, Reetz J, Brandes S, Dai Z, Putzer BM et al (2016) Direct reprogramming of hepatic myofibroblasts into hepatocytes in vivo attenuates liver fibrosis. Cell Stem Cell 18:797–808

    Article  CAS  PubMed  Google Scholar 

  6. Reetz J, Genz B, Meier C, Kowtharapu BS, Timm F, Vollmar B, Herchenroder O, Abshagen K, Putzer BM (2013) Development of adenoviral delivery systems to target hepatic stellate cells in vivo. PLoS One 8:e67091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Mederacke I, Hsu CC, Troeger JS, Huebener P, Mu X, Dapito DH, Pradere JP, Schwabe RF (2013) Fate tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its aetiology. Nat Commun 4:2823

    Article  PubMed  PubMed Central  Google Scholar 

  8. Armendariz-Borunda J, Bastidas-Ramirez BE, Sandoval-Rodriguez A, Gonzalez-Cuevas J, Gomez-Meda B, Garcia-Banuelos J (2011) Production of first generation adenoviral vectors for preclinical protocols: amplification, purification and functional titration. J Biosci Bioeng 112:415–421

    Article  CAS  PubMed  Google Scholar 

  9. Yuan Q, Loya K, Rani B, Mobus S, Balakrishnan A, Lamle J, Cathomen T, Vogel A, Manns MP, Ott M et al (2013) MicroRNA-221 overexpression accelerates hepatocyte proliferation during liver regeneration. Hepatology 57:299–310

    Article  CAS  PubMed  Google Scholar 

  10. Bartneck M, Warzecha KT, Tag CG, Sauer-Lehnen S, Heymann F, Trautwein C, Weiskirchen R, Tacke F (2015) Isolation and time lapse microscopy of highly pure hepatic stellate cells. Anal Cell Pathol (Amst) 2015:417023

    Google Scholar 

  11. Weiskirchen R, Gressner AM (2005) Isolation and culture of hepatic stellate cells. Methods Mol Med 117:99–113

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Guangqi Song .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Song, G. et al. (2019). Conversion of Fibroblasts to Hepatocyte-Like Cells In Vivo. In: Tanimizu, N. (eds) Hepatic Stem Cells . Methods in Molecular Biology, vol 1905. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8961-4_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-8961-4_10

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8960-7

  • Online ISBN: 978-1-4939-8961-4

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics