Therapeutic potential of amniotic-fluid-derived stem cells on liver fibrosis model in mice

Shao-Yu Peng; Chih-Jen Chou; Po-Jen Cheng; I-Chen Ko; Yi-Jung Kao; Yu-Hsu Chen; Winston Teng-Kui Cheng; S W Steven Shaw; Shinn-Chih Wu

doi:10.1016/j.tjog.2014.04.005

Therapeutic potential of amniotic-fluid-derived stem cells on liver fibrosis model in mice

Taiwan J Obstet Gynecol. 2014 Jun;53(2):151-7. doi: 10.1016/j.tjog.2014.04.005.

Authors

Shao-Yu Peng¹, Chih-Jen Chou¹, Po-Jen Cheng², I-Chen Ko³, Yi-Jung Kao³, Yu-Hsu Chen⁴, Winston Teng-Kui Cheng⁵, S W Steven Shaw⁶, Shinn-Chih Wu⁷

Affiliations

¹ Institute of Biotechnology, National Taiwan University, Taipei, Taiwan.
² Department of Obstetrics and Gynaecology, Chang Gung Memorial Hospital at Linkou and Chang Gung University, College of Medicine, Taoyuan, Taiwan.
³ Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan.
⁴ Institute of Biotechnology, National Taiwan University, Taipei, Taiwan; Department of Surgery, Hualien Armed Forces General Hospital, Hualien, Taiwan.
⁵ Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan; Department of Animal Science and Biotechnology, Tunghai University, Taichung, Taiwan.
⁶ Department of Obstetrics and Gynaecology, Chang Gung Memorial Hospital at Linkou and Chang Gung University, College of Medicine, Taoyuan, Taiwan; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan; Prenatal Cell and Gene Therapy Group, Institute for Women's Health, University College London, London, UK. Electronic address: dr.shaw@me.com.
⁷ Institute of Biotechnology, National Taiwan University, Taipei, Taiwan; Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan. Electronic address: scw01@ntu.edu.tw.

PMID: 25017258
DOI: 10.1016/j.tjog.2014.04.005

Abstract

Objective: Liver fibrosis results from the wound healing response to chronic liver damage. Advanced liver fibrosis results in cirrhosis and liver failure, and liver transplantation is often the only option for effective therapy; however, the shortage of available donor livers limits this treatment. Thus, new therapies for advanced liver fibrosis are essential.

Materials and methods: Amniotic fluid contains an abundance of stem cells, which are derived from all three germ layers of the developing fetus. These cells do not induce teratomas in vivo and do not pose any ethical concerns. To generate liver fibrosis models, male ICR mice were treated with CCl4 via oral gavage for 4 weeks, and the serum levels of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and albumin were higher than in the control group following chemical induction. To assess the potential of amniotic-fluid-derived stem cells (mAFSCs) to ameliorate liver fibrosis in vivo, mAFSCs were isolated from amniotic fluid of 13.5-day-old transgenic mice, which globally express the fluorescent protein, enhanced green fluorescent protein (EGFP), for tracing purposes (EGFP-mAFSCs). Single cells were injected via the mesentery (1 × 10(6) cells/mouse) of transplanted mice with liver fibrosis.

Results: Four weeks after EGFP-mAFSC transplantation, the serum glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and albumin levels of recipient mice in the EGFP-mAFSC-injected group were significantly decreased when compared with mice in the saline-injected group. Additionally, fibrotic tissues were evaluated using Masson's trichrome staining 4 weeks after cell transplantation. Shrinkage of the fibrotic area was observed in the EGFP-mAFSC-injected group. The tissue-repair effects were also confirmed by hydroxyproline content analysis.

Conclusion: The possible repair mechanism from our data revealed that EGFP-mAFSCs may fuse with the recipient liver cells. Overall, EGFP-mAFSCs can ameliorate liver fibrosis in mice, thus providing insight into the future development of regenerative medicine.

Keywords: amniotic-fluid-derived stem cells; liver fibrosis; mice; transplantation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alanine Transaminase / blood
Amniotic Fluid / cytology*
Animals
Aspartate Aminotransferases / blood
Carbon Tetrachloride
Disease Models, Animal
Fetal Stem Cells / transplantation*
Hydroxyproline / analysis
Liver / chemistry
Liver Cirrhosis / blood
Liver Cirrhosis / chemically induced
Liver Cirrhosis / pathology
Liver Cirrhosis / therapy*
Male
Mice
Mice, Inbred ICR
Serum Albumin / metabolism

Substances

Serum Albumin
Carbon Tetrachloride
Aspartate Aminotransferases
Alanine Transaminase
Hydroxyproline