Hepatocyte Growth Factor Gene-Modified Adipose-Derived Mesenchymal Stem Cells Ameliorate Radiation Induced Liver Damage in a Rat Model

被引:54
作者
Zhang, Jiamin [1 ]
Zhou, Shiyuan [1 ]
Zhou, Yi [1 ]
Feng, Feier [1 ]
Wang, Qianming [1 ]
Zhu, Xiaolu [1 ]
Ai, Huisheng [2 ]
Huang, Xiaojun [1 ]
Zhang, Xiaohui [1 ]
机构
[1] Peking Univ, Inst Hematol, Peking Univ Peoples Hosp, Beijing 100871, Peoples R China
[2] Acad Mil Med Sci, Affiliated Hosp, Dept Hematol, Beijing, Peoples R China
基金
北京市自然科学基金; 中国国家自然科学基金;
关键词
UMBILICAL-CORD BLOOD; BONE-MARROW; IN-VITRO; STROMAL CELLS; INJURY; TISSUE; IRRADIATION; DIFFERENTIATION; TRANSPLANTATION; FIBROSIS;
D O I
10.1371/journal.pone.0114670
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 alpha-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.
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页数:20
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