The therapeutic potential of induced hepatocyte-like cells generated by direct reprogramming on hepatic fibrosis
Abstract Background Until now, there is no effective anti-fibrotic therapy available for liver cirrhosis. Stem cell therapies have been studied for the treatment of hepatic fibrosis. However, the use of embryonic stem cells or induced pluripotent stem cells (iPSC) has limitations such as ethical con...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2019-01-01
|
Series: | Stem Cell Research & Therapy |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s13287-018-1127-3 |
id |
doaj-b9abae80e7dc430ba6a3c0e87747de67 |
---|---|
record_format |
Article |
spelling |
doaj-b9abae80e7dc430ba6a3c0e87747de672020-11-25T02:48:46ZengBMCStem Cell Research & Therapy1757-65122019-01-0110111110.1186/s13287-018-1127-3The therapeutic potential of induced hepatocyte-like cells generated by direct reprogramming on hepatic fibrosisSuhyun Park0Seon In Hwang1Jonghun Kim2Seoyeon Hwang3Sohee Kang4Sera Yang5Jonghwa Kim6Wonseok Kang7Kyun-Hwan Kim8Dong Wook Han9Yong-Han Paik10Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of MedicineDepartment of Stem Cell Biology, School of Medicine, Konkuk UniversityDepartment of Stem Cell Biology, School of Medicine, Konkuk UniversityDepartment of Medicine, Samsung Medical Center, Sungkyunkwan University School of MedicineDepartment of Medicine, Samsung Medical Center, Sungkyunkwan University School of MedicineDepartment of Medicine, Samsung Medical Center, Sungkyunkwan University School of MedicineDepartment of Medicine, Samsung Medical Center, Sungkyunkwan University School of MedicineDepartment of Medicine, Samsung Medical Center, Sungkyunkwan University School of MedicineKonkuk University Open Innovation Center, Research Institute of Medical Sciences, Konkuk UniversityDepartment of Stem Cell Biology, School of Medicine, Konkuk UniversityDepartment of Medicine, Samsung Medical Center, Sungkyunkwan University School of MedicineAbstract Background Until now, there is no effective anti-fibrotic therapy available for liver cirrhosis. Stem cell therapies have been studied for the treatment of hepatic fibrosis. However, the use of embryonic stem cells or induced pluripotent stem cells (iPSC) has limitations such as ethical concern or malignancy potential. Induced hepatocyte-like cells (iHEPs) generated by direct reprogramming technology may overcome these limitations. Methods In this study, we generated iHEPs by direct reprogramming from mouse embryonic fibroblast (MEF) either using specific transcription factors such as c-Myc and Klf-4 (type A), or adding small molecules to HNF1α (type B). Results We investigated the effect of iHEPs on acute liver injury and chronic hepatic fibrosis animal models induced by CCl4 intra-peritoneal injection in BALB/C nude mice. In acute liver injury model, serum AST/ALT levels peaked at 24 h after CCl4 injection. Intra-splenic transplantation of iHEPs significantly attenuated CCl4-induced acute liver injury. GFP-labeled iHEPs (type A) migrated to the liver after intra-splenic transplantation that was confirmed by Western blotting and immunofluorescence staining. We found that GFP and albumin were co-localized in migrated iHEPs in the liver suggesting migrated iHEPs were functional. In chronic hepatic fibrosis mice experiment, transplantation of either type A or type B iHEPs significantly attenuated liver fibrosis induced by CCl4 injection for 10 weeks. Conclusions Our study suggests that iHEPs may be used as a novel therapeutic strategy for the treatment of hepatic fibrosis.http://link.springer.com/article/10.1186/s13287-018-1127-3Animal modelsDisease modelingCCl4Stem cell transplantationHepatic fibrosisCell and tissue-based therapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Suhyun Park Seon In Hwang Jonghun Kim Seoyeon Hwang Sohee Kang Sera Yang Jonghwa Kim Wonseok Kang Kyun-Hwan Kim Dong Wook Han Yong-Han Paik |
spellingShingle |
Suhyun Park Seon In Hwang Jonghun Kim Seoyeon Hwang Sohee Kang Sera Yang Jonghwa Kim Wonseok Kang Kyun-Hwan Kim Dong Wook Han Yong-Han Paik The therapeutic potential of induced hepatocyte-like cells generated by direct reprogramming on hepatic fibrosis Stem Cell Research & Therapy Animal models Disease modeling CCl4 Stem cell transplantation Hepatic fibrosis Cell and tissue-based therapy |
author_facet |
Suhyun Park Seon In Hwang Jonghun Kim Seoyeon Hwang Sohee Kang Sera Yang Jonghwa Kim Wonseok Kang Kyun-Hwan Kim Dong Wook Han Yong-Han Paik |
author_sort |
Suhyun Park |
title |
The therapeutic potential of induced hepatocyte-like cells generated by direct reprogramming on hepatic fibrosis |
title_short |
The therapeutic potential of induced hepatocyte-like cells generated by direct reprogramming on hepatic fibrosis |
title_full |
The therapeutic potential of induced hepatocyte-like cells generated by direct reprogramming on hepatic fibrosis |
title_fullStr |
The therapeutic potential of induced hepatocyte-like cells generated by direct reprogramming on hepatic fibrosis |
title_full_unstemmed |
The therapeutic potential of induced hepatocyte-like cells generated by direct reprogramming on hepatic fibrosis |
title_sort |
therapeutic potential of induced hepatocyte-like cells generated by direct reprogramming on hepatic fibrosis |
publisher |
BMC |
series |
Stem Cell Research & Therapy |
issn |
1757-6512 |
publishDate |
2019-01-01 |
description |
Abstract Background Until now, there is no effective anti-fibrotic therapy available for liver cirrhosis. Stem cell therapies have been studied for the treatment of hepatic fibrosis. However, the use of embryonic stem cells or induced pluripotent stem cells (iPSC) has limitations such as ethical concern or malignancy potential. Induced hepatocyte-like cells (iHEPs) generated by direct reprogramming technology may overcome these limitations. Methods In this study, we generated iHEPs by direct reprogramming from mouse embryonic fibroblast (MEF) either using specific transcription factors such as c-Myc and Klf-4 (type A), or adding small molecules to HNF1α (type B). Results We investigated the effect of iHEPs on acute liver injury and chronic hepatic fibrosis animal models induced by CCl4 intra-peritoneal injection in BALB/C nude mice. In acute liver injury model, serum AST/ALT levels peaked at 24 h after CCl4 injection. Intra-splenic transplantation of iHEPs significantly attenuated CCl4-induced acute liver injury. GFP-labeled iHEPs (type A) migrated to the liver after intra-splenic transplantation that was confirmed by Western blotting and immunofluorescence staining. We found that GFP and albumin were co-localized in migrated iHEPs in the liver suggesting migrated iHEPs were functional. In chronic hepatic fibrosis mice experiment, transplantation of either type A or type B iHEPs significantly attenuated liver fibrosis induced by CCl4 injection for 10 weeks. Conclusions Our study suggests that iHEPs may be used as a novel therapeutic strategy for the treatment of hepatic fibrosis. |
topic |
Animal models Disease modeling CCl4 Stem cell transplantation Hepatic fibrosis Cell and tissue-based therapy |
url |
http://link.springer.com/article/10.1186/s13287-018-1127-3 |
work_keys_str_mv |
AT suhyunpark thetherapeuticpotentialofinducedhepatocytelikecellsgeneratedbydirectreprogrammingonhepaticfibrosis AT seoninhwang thetherapeuticpotentialofinducedhepatocytelikecellsgeneratedbydirectreprogrammingonhepaticfibrosis AT jonghunkim thetherapeuticpotentialofinducedhepatocytelikecellsgeneratedbydirectreprogrammingonhepaticfibrosis AT seoyeonhwang thetherapeuticpotentialofinducedhepatocytelikecellsgeneratedbydirectreprogrammingonhepaticfibrosis AT soheekang thetherapeuticpotentialofinducedhepatocytelikecellsgeneratedbydirectreprogrammingonhepaticfibrosis AT serayang thetherapeuticpotentialofinducedhepatocytelikecellsgeneratedbydirectreprogrammingonhepaticfibrosis AT jonghwakim thetherapeuticpotentialofinducedhepatocytelikecellsgeneratedbydirectreprogrammingonhepaticfibrosis AT wonseokkang thetherapeuticpotentialofinducedhepatocytelikecellsgeneratedbydirectreprogrammingonhepaticfibrosis AT kyunhwankim thetherapeuticpotentialofinducedhepatocytelikecellsgeneratedbydirectreprogrammingonhepaticfibrosis AT dongwookhan thetherapeuticpotentialofinducedhepatocytelikecellsgeneratedbydirectreprogrammingonhepaticfibrosis AT yonghanpaik thetherapeuticpotentialofinducedhepatocytelikecellsgeneratedbydirectreprogrammingonhepaticfibrosis AT suhyunpark therapeuticpotentialofinducedhepatocytelikecellsgeneratedbydirectreprogrammingonhepaticfibrosis AT seoninhwang therapeuticpotentialofinducedhepatocytelikecellsgeneratedbydirectreprogrammingonhepaticfibrosis AT jonghunkim therapeuticpotentialofinducedhepatocytelikecellsgeneratedbydirectreprogrammingonhepaticfibrosis AT seoyeonhwang therapeuticpotentialofinducedhepatocytelikecellsgeneratedbydirectreprogrammingonhepaticfibrosis AT soheekang therapeuticpotentialofinducedhepatocytelikecellsgeneratedbydirectreprogrammingonhepaticfibrosis AT serayang therapeuticpotentialofinducedhepatocytelikecellsgeneratedbydirectreprogrammingonhepaticfibrosis AT jonghwakim therapeuticpotentialofinducedhepatocytelikecellsgeneratedbydirectreprogrammingonhepaticfibrosis AT wonseokkang therapeuticpotentialofinducedhepatocytelikecellsgeneratedbydirectreprogrammingonhepaticfibrosis AT kyunhwankim therapeuticpotentialofinducedhepatocytelikecellsgeneratedbydirectreprogrammingonhepaticfibrosis AT dongwookhan therapeuticpotentialofinducedhepatocytelikecellsgeneratedbydirectreprogrammingonhepaticfibrosis AT yonghanpaik therapeuticpotentialofinducedhepatocytelikecellsgeneratedbydirectreprogrammingonhepaticfibrosis |
_version_ |
1724746855484489728 |