title: Hepatocyte growth factor gene-modified adipose-derived mesenchymal stem cells ameliorate radiation induced liver damage in a rat model.
abstract: Liver damage caused by radiotherapy is associated with a high mortality rate, but no established treatment exists. Adipose-derived mesenchymal stem cells (ADSCs) are capable of migration to injured tissue sites, where they aid in the repair of the damage. Hepatocyte growth factor (HGF) is critical for damage repair due to its anti-apoptotic, anti-fibrotic and cell regeneration-promoting effects. This study was performed to investigate the therapeutic effects of HGF-overexpressing ADSCs on radiation-induced liver damage (RILD). ADSCs were infected with a lentivirus encoding HGF and HGF-shRNA. Sprague-Dawley (SD) rats received 60Gy of irradiation to induce liver injury and were immediately given either saline, ADSCs, ADSCs + HGF or ADSCs + shHGF. Two days after irradiation, a significant reduction in apoptosis was observed in the HGF-overexpressing ADSC group compared with the RILD group, as assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Scanning electron microscopy showed chromatin condensation after irradiation, which was ameliorated in the group that received ADSCs and was reversed in the group that received HGF-overexpressing ADSCs. HGF-overexpressing ADSCs ameliorated radiation- induced liver fibrosis through down regulation of α-SMA and fibronectin. Hepatocyte regeneration was significantly improved in rats treated with ADSCs compared with rats from the RILD group), as assessed by Ki-67 immunohistochemistry. Rats that received HGF-overexpressing ADSCs showed an even greater level of hepatocyte regeneration. HGF-overexpressing ADSCs completely blocked the radiation-induced increase in the enzymes ALT and AST. The effect of mitigating RILD was compromised in the ADSC + shHGF group compared with the ADSC group. Altogether, these results suggest that HGF-overexpressing ADSCs can significantly improve RILD in a rat model, which may serve as a valuable therapeutic alternative.
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Xicheng District, Beijing, China.
authors.forename: Jiamin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Xicheng District, Beijing, China.
authors.forename: Shiyuan
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Xicheng District, Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Xicheng District, Beijing, China.
authors.forename: Feier
authors.initials: F
authors.lastname: Feng
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Xicheng District, Beijing, China.
authors.forename: Qianming
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Xicheng District, Beijing, China.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Hematology, Affiliated Hospital to the Academy of Military Medicine Science, FengTai District, Beijing, China.
authors.forename: Huisheng
authors.initials: H
authors.lastname: Ai
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Xicheng District, Beijing, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Huang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Xicheng District, Beijing, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D004195:Disease Models, Animal; D005355:Fibrosis; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D022781:Hepatocytes / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects; D008115:Liver Regeneration; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D017228:Hepatocyte Growth Factor