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

Research output: Contribution to journalArticlepeer-review

2 Citations (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

Bibliographical note

Funding Information:
This research was supported by Grants from the Medical Research Center (NRF-2017R1A5A2015395) and Basic Science Research Program (2017R1D1A1B03030508), funded by

Funding Information:
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.

Publisher Copyright:
© 2018 Sangtae Yoon et al.

ASJC Scopus subject areas

  • General Immunology and Microbiology
  • General Biochemistry,Genetics and Molecular Biology

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