Generation of integration-free induced hepatocyte-like cells from mouse fibroblasts

Jonghun Kim; Kee Pyo Kim; Kyung Tae Lim; Seung Chan Lee; Juyong Yoon; Guangqi Song; Seon In Hwang; Hans R. Schöler; Tobias Cantz; Dong Wook Han

doi:10.1038/srep15706

Generation of integration-free induced hepatocyte-like cells from mouse fibroblasts

Jonghun Kim
, Kee Pyo Kim
, Kyung Tae Lim
, Seung Chan Lee
, Juyong Yoon
, Guangqi Song
, Seon In Hwang
, Hans R. Schöler
, Tobias Cantz
, Dong Wook Han

Department of Biomedicine & Health Science

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

Abstract

The ability to generate integration-free induced hepatocyte-like cells (iHeps) from somatic fibroblasts has the potential to advance their clinical application. Here, we have generated integration-free, functional, and expandable iHeps from mouse somatic fibroblasts. To elicit this direct conversion, we took advantage of an oriP/EBNA1-based episomal system to deliver a set of transcription factors, Gata4, Hnf1a, and Foxa3, to the fibroblasts. The established iHeps exhibit similar morphology, marker expression, and functional properties to primary hepatocytes. Furthermore, integration-free iHeps prolong the survival of fumarylacetoacetate-hydrolase-deficient (Fah -/-) mice after cell transplantation. Our study provides a novel concept for generating functional and expandable iHeps using a non-viral, non-integrating, plasmid-based system that could facilitate their pharmaceutical and biomedical application.

Original language	English
Article number	15706
Journal	Scientific Reports
Volume	5
DOIs	https://doi.org/10.1038/srep15706
State	Published - 27 Oct 2015

Bibliographical note

Funding Information:
This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (2011-0013885); the Bio & Medical Technology Development Program of the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (2011-0019490); and by a grant from the Next-Generation BioGreen21 program (PJ011311), Rural Development Administration, Republic of Korea.

Access to Document

10.1038/srep15706

Cite this

@article{f0f1d47c2c2e4f11aba1a466ea31e5ad,

title = "Generation of integration-free induced hepatocyte-like cells from mouse fibroblasts",

abstract = "The ability to generate integration-free induced hepatocyte-like cells (iHeps) from somatic fibroblasts has the potential to advance their clinical application. Here, we have generated integration-free, functional, and expandable iHeps from mouse somatic fibroblasts. To elicit this direct conversion, we took advantage of an oriP/EBNA1-based episomal system to deliver a set of transcription factors, Gata4, Hnf1a, and Foxa3, to the fibroblasts. The established iHeps exhibit similar morphology, marker expression, and functional properties to primary hepatocytes. Furthermore, integration-free iHeps prolong the survival of fumarylacetoacetate-hydrolase-deficient (Fah -/-) mice after cell transplantation. Our study provides a novel concept for generating functional and expandable iHeps using a non-viral, non-integrating, plasmid-based system that could facilitate their pharmaceutical and biomedical application.",

author = "Jonghun Kim and Kim, \{Kee Pyo\} and Lim, \{Kyung Tae\} and Lee, \{Seung Chan\} and Juyong Yoon and Guangqi Song and Hwang, \{Seon In\} and Sch{\"o}ler, \{Hans R.\} and Tobias Cantz and Han, \{Dong Wook\}",

note = "Funding Information: This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (2011-0013885); the Bio \& Medical Technology Development Program of the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (2011-0019490); and by a grant from the Next-Generation BioGreen21 program (PJ011311), Rural Development Administration, Republic of Korea.",

year = "2015",

month = oct,

day = "27",

doi = "10.1038/srep15706",

language = "English",

volume = "5",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Research",

}

TY - JOUR

T1 - Generation of integration-free induced hepatocyte-like cells from mouse fibroblasts

AU - Kim, Jonghun

AU - Kim, Kee Pyo

AU - Lim, Kyung Tae

AU - Lee, Seung Chan

AU - Yoon, Juyong

AU - Song, Guangqi

AU - Hwang, Seon In

AU - Schöler, Hans R.

AU - Cantz, Tobias

AU - Han, Dong Wook

N1 - Funding Information: This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (2011-0013885); the Bio & Medical Technology Development Program of the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (2011-0019490); and by a grant from the Next-Generation BioGreen21 program (PJ011311), Rural Development Administration, Republic of Korea.

PY - 2015/10/27

Y1 - 2015/10/27

N2 - The ability to generate integration-free induced hepatocyte-like cells (iHeps) from somatic fibroblasts has the potential to advance their clinical application. Here, we have generated integration-free, functional, and expandable iHeps from mouse somatic fibroblasts. To elicit this direct conversion, we took advantage of an oriP/EBNA1-based episomal system to deliver a set of transcription factors, Gata4, Hnf1a, and Foxa3, to the fibroblasts. The established iHeps exhibit similar morphology, marker expression, and functional properties to primary hepatocytes. Furthermore, integration-free iHeps prolong the survival of fumarylacetoacetate-hydrolase-deficient (Fah -/-) mice after cell transplantation. Our study provides a novel concept for generating functional and expandable iHeps using a non-viral, non-integrating, plasmid-based system that could facilitate their pharmaceutical and biomedical application.

AB - The ability to generate integration-free induced hepatocyte-like cells (iHeps) from somatic fibroblasts has the potential to advance their clinical application. Here, we have generated integration-free, functional, and expandable iHeps from mouse somatic fibroblasts. To elicit this direct conversion, we took advantage of an oriP/EBNA1-based episomal system to deliver a set of transcription factors, Gata4, Hnf1a, and Foxa3, to the fibroblasts. The established iHeps exhibit similar morphology, marker expression, and functional properties to primary hepatocytes. Furthermore, integration-free iHeps prolong the survival of fumarylacetoacetate-hydrolase-deficient (Fah -/-) mice after cell transplantation. Our study provides a novel concept for generating functional and expandable iHeps using a non-viral, non-integrating, plasmid-based system that could facilitate their pharmaceutical and biomedical application.

UR - https://www.scopus.com/pages/publications/84945920571

U2 - 10.1038/srep15706

DO - 10.1038/srep15706

M3 - Article

C2 - 26503743

AN - SCOPUS:84945920571

SN - 2045-2322

VL - 5

JO - Scientific Reports

JF - Scientific Reports

M1 - 15706

ER -

Generation of integration-free induced hepatocyte-like cells from mouse fibroblasts

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Cite this