Nonintegrating direct conversion using mRNA into hepatocyte-like cells

Sangtae Yoon, Kyojin Kang, Young Duck Cho, Yohan Kim, Elina Maria Buisson, Ji Hye Yim, Seung Bum Lee, Ki Young Ryu, Jaemin Jeong, Dongho Choi

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1 Citation (Scopus)

Abstract

Recently, several researchers have reported that direct reprogramming techniques can be used to differentiate fibroblasts into hepatocyte-like cells without a pluripotent intermediate step. However, the use of viral vectors for conversion continues to pose important challenges in terms of genome integration. Herein, we propose a new method of direct conversion without genome integration with potential clinical applications. To generate hepatocyte-like cells, mRNA coding for the hepatic transcription factors Foxa3 and HNF4α was transfected into mouse embryonic fibroblasts. After 10-12 days, the fibroblasts converted to an epithelial morphology and generated colonies of hepatocyte-like cells (R-iHeps). The generated R-iHeps expressed hepatocyte-specific marker genes and proteins, including albumin, alpha-fetoprotein, HNF4α, CK18, and CYP1A2. To evaluate hepatic function, indocyanine green uptake, periodic acid-Schiff staining, and albumin secretion were assessed. Furthermore, mCherry-positive R-iHeps were engrafted in the liver of Alb-TRECK/SCID mice, and we confirmed FAH enzyme expression in Fah1RTyrc/RJ models. In conclusion, our data suggest that the nonintegrating method using mRNA has potential for cell therapy.

Original languageEnglish
Article number8240567
JournalBioMed Research International
Volume2018
DOIs
Publication statusPublished - 2018 Jan 1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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  • Cite this

    Yoon, S., Kang, K., Cho, Y. D., Kim, Y., Buisson, E. M., Yim, J. H., Lee, S. B., Ryu, K. Y., Jeong, J., & Choi, D. (2018). Nonintegrating direct conversion using mRNA into hepatocyte-like cells. BioMed Research International, 2018, [8240567]. https://doi.org/10.1155/2018/8240567