Transplantation of bone marrow-derived mesenchymal stem cells after regional hepatic irradiation ameliorates thioacetamide-induced liver fibrosis in rats.
BACKGROUND
Recent studies have demonstrated that bone marrow-derived mesenchymal stem cells (BM-MSCs) can potentially revert liver fibrosis, but it is not known if preparative hepatic irradiation (HIR) contributes to the therapeutic effect of transplanted BM-MSCs. In this study, we investigate the effects of HIR on transplanted BM-MSCs in cirrhotic rats and the underlying mechanism by which mesenchymal stem cells (MSCs) relieve liver fibrosis.


METHODS
The BM-MSCs from male rats were labeled with CM-Dil and injected via portal vein into two groups of thioacetamide-induced cirrhotic rats, and the controls were injected with the same volume of saline. The right hemiliver of one cirrhotic rat group was irradiated (15 Gy) 4 d before transplantation. Liver function tests and histologic experiments were performed, and the liver population of BM-MSCs was estimated.


RESULTS
The transplantation of MSCs alleviated liver fibrosis and reduced expression of transforming growth factor-β1, Smad2, collagen type I, and α-SMA. HIR preconditioning promoted homing and repopulation of MSCs and resulted in better treatment outcomes.


CONCLUSIONS
HIR preconditioning enhances the effect of BM-MSCs in improving thioacetamide-induced liver fibrosis in rats by promoting their homing and repopulation. BM-MSCs may function by inhibiting transforming growth factor-β1-Smad signaling pathway in the liver.
Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China; Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, Jiangsu Province, China.
Cun-hua
CH
Shao
Sheng-lin
SL
Chen
Tian-fu
TF
Dong
Hao
H
Chai
Yue
Y
Yu
Lei
L
Deng
Yun
Y
Wang
Feng
F
Cheng
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D008099:Liver / Q000528:radiation effects*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051785:Smad Proteins / Q000502:physiology; D013853:Thioacetamide / Q000633:toxicity; D053773:Transforming Growth Factor beta1 / Q000502:physiology
D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D013853:Thioacetamide
Bone marrow–derived mesenchymal stem cells; Hepatic irradiation; Liver fibrosis; Transforming growth factor-β1