Hepatocyte growth factor modification promotes the amelioration effects of human umbilical cord mesenchymal stem cells on rat acute kidney injury.
Human umbilical cord-derived mesenchymal stem cells (hucMSCs) are particularly attractive cells for cellular and gene therapy in acute kidney injury (AKI). Adenovirus-mediated gene therapy has been limited by immune reaction and target genes selection. However, in the present study, we investigated the therapeutic effects of hepatocyte growth factor modified hucMSCs (HGF-hucMSCs) in ischemia/reperfusion-induced AKI rat models. In vivo animal models were generated by subjecting to 60 min of bilateral renal injury by clamping the renal pedicles and then introduced HGF-hucMSCs via the left carotid artery. Our results revealed that serum creatinine and urea nitrogen levels decreased to the baseline more quickly in HGF-hucMSCs-treated group than that in hucMSCs- or green fluorescent protein-hucMSCs-treated groups at 72 h after injury. The percent of proliferating cell nuclear antigen-positive cells in HGF-hucMSCs-treated group was higher than that in the hucMSCs or green fluorescent protein-hucMSCs-treated groups. Moreover, injured renal tissues treated with HGF-hucMSCs also exhibited less hyperemia and renal tubule cast during the recovery process. Immunohistochemistry and living body imaging confirmed that HGF-hucMSCs localize to areas of renal injury. Real-time polymerase chain reaction result showed that HGF-hucMSCs also inhibited caspase-3 and interleukin-1β mRNA expression in injured renal tissues. Western blot also showed HGF-hucMSCs-treated groups had lower expression of interleukin-1β. Terminal deoxynucleotidyl transferase biotin-deoxyuridine triphosphate (dUTP) nick end labeling method indicated that HGF-hucMSCs-treated group had the least apoptosis cells. In conclusion, our findings suggest that HGF modification promotes the amelioration of ischemia/reperfusion-induced rat renal injury via antiapoptotic and antiinflammatory mechanisms; thus, providing a novel therapeutic application for hucMSCs in AKI.
Chen
Yuan
Y
Jiangsu University, Zhenjiang, People's Republic of China.
Qian
Hui
H
Zhu
Wei
W
Zhang
Xu
X
Yan
Yongmin
Y
Ye
Shengqin
S
Peng
Xiujuan
X
Li
Wei
W
Xu
Wenrong
W
D058186:Acute Kidney Injury / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D049109:Cell Proliferation; D005260:Female; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000473:pathology; D007668:Kidney / Q000473:pathology; D007677:Kidney Function Tests; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D009369:Neoplasms / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000503:physiopathology; D014161:Transduction, Genetic; D014470:Umbilical Cord / Q000166:cytology*
D017228:Hepatocyte Growth Factor