PMID- 20446811 OWN - NLM STAT- MEDLINE DCOM- 20110415 LR - 20181201 IS - 1557-8534 (Electronic) IS - 1547-3287 (Linking) VI - 20 IP - 1 DP - 2011 Jan TI - Hepatocyte growth factor modification promotes the amelioration effects of human umbilical cord mesenchymal stem cells on rat acute kidney injury. PG - 103-13 LID - 10.1089/scd.2009.0495 [doi] AB - 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-1beta mRNA expression in injured renal tissues. Western blot also showed HGF-hucMSCs-treated groups had lower expression of interleukin-1beta. 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. FAU - Chen, Yuan AU - Chen Y AD - Jiangsu University, Zhenjiang, People's Republic of China. FAU - Qian, Hui AU - Qian H FAU - Zhu, Wei AU - Zhu W FAU - Zhang, Xu AU - Zhang X FAU - Yan, Yongmin AU - Yan Y FAU - Ye, Shengqin AU - Ye S FAU - Peng, Xiujuan AU - Peng X FAU - Li, Wei AU - Li W FAU - Xu, Wenrong AU - Xu W LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101012 PL - United States TA - Stem Cells Dev JT - Stem cells and development JID - 101197107 RN - 67256-21-7 (Hepatocyte Growth Factor) SB - IM MH - Acute Kidney Injury/complications/physiopathology/*therapy MH - Adenoviridae/genetics MH - Animals MH - Apoptosis MH - Cell Cycle MH - Cell Proliferation MH - Female MH - Gene Expression Regulation MH - Genetic Vectors MH - Hepatocyte Growth Factor/*metabolism MH - Humans MH - Inflammation/complications/pathology MH - Kidney/pathology MH - Kidney Function Tests MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/*cytology/*metabolism MH - Neoplasms/pathology MH - Rats MH - Rats, Sprague-Dawley MH - Reperfusion Injury/complications/physiopathology MH - Transduction, Genetic MH - Umbilical Cord/*cytology EDAT- 2010/05/08 06:00 MHDA- 2011/04/19 06:00 CRDT- 2010/05/08 06:00 PHST- 2010/05/08 06:00 [entrez] PHST- 2010/05/08 06:00 [pubmed] PHST- 2011/04/19 06:00 [medline] AID - 10.1089/scd.2009.0495 [doi] PST - ppublish SO - Stem Cells Dev. 2011 Jan;20(1):103-13. doi: 10.1089/scd.2009.0495. Epub 2010 Oct 12.