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学科主题临床医学
Hepatocyte Growth Factor Gene-Modified Adipose-Derived Mesenchymal Stem Cells Ameliorate Radiation Induced Liver Damage in a Rat Model
Zhang, Jiamin1; Zhou, Shiyuan1; Zhou, Yi1; Feng, Feier1; Wang, Qianming1; Zhu, Xiaolu1; Ai, Huisheng2; Huang, Xiaojun1; Zhang, Xiaohui1
刊名PLOS ONE
2014-12-12
DOI10.1371/journal.pone.0114670
9期:12
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]UMBILICAL-CORD BLOOD ; BONE-MARROW ; IN-VITRO ; STROMAL CELLS ; INJURY ; TISSUE ; IRRADIATION ; DIFFERENTIATION ; TRANSPLANTATION ; FIBROSIS
英文摘要

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.

语种英语
WOS记录号WOS:000346375400044
项目编号2012BAI38B03 ; 81270643 ; 81470343 ; 2141000008 ; 7132194 ; 20120001110026
资助机构National Key Technology Support Program ; National Natural Science Foundation of China ; Seeding Grant for Medicine and Engineering Sciences of Peking University ; Beijing Natural Science Foundation ; Specialized Research Fund for the Doctoral Program of Higher Education
引用统计
被引频次:18[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/55596
专题北京大学第二临床医学院_血液科
作者单位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
推荐引用方式
GB/T 7714
Zhang, Jiamin,Zhou, Shiyuan,Zhou, Yi,et al. Hepatocyte Growth Factor Gene-Modified Adipose-Derived Mesenchymal Stem Cells Ameliorate Radiation Induced Liver Damage in a Rat Model[J]. PLOS ONE,2014,9(12).
APA Zhang, Jiamin.,Zhou, Shiyuan.,Zhou, Yi.,Feng, Feier.,Wang, Qianming.,...&Zhang, Xiaohui.(2014).Hepatocyte Growth Factor Gene-Modified Adipose-Derived Mesenchymal Stem Cells Ameliorate Radiation Induced Liver Damage in a Rat Model.PLOS ONE,9(12).
MLA Zhang, Jiamin,et al."Hepatocyte Growth Factor Gene-Modified Adipose-Derived Mesenchymal Stem Cells Ameliorate Radiation Induced Liver Damage in a Rat Model".PLOS ONE 9.12(2014).
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