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Hepatocyte growth factor modification promotes the amelioration effects of human umbilical cord mesenchymal stem cells on rat acute kidney injury.

Abstract
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.
AuthorsYuan Chen, Hui Qian, Wei Zhu, Xu Zhang, Yongmin Yan, Shengqin Ye, Xiujuan Peng, Wei Li, Wenrong Xu
JournalStem cells and development (Stem Cells Dev) Vol. 20 Issue 1 Pg. 103-13 (Jan 2011) ISSN: 1557-8534 [Electronic] United States
PMID20446811 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Hepatocyte Growth Factor
Topics
  • Acute Kidney Injury (complications, physiopathology, therapy)
  • Adenoviridae (genetics)
  • Animals
  • Apoptosis
  • Cell Cycle
  • Cell Proliferation
  • Female
  • Gene Expression Regulation
  • Genetic Vectors
  • Hepatocyte Growth Factor (metabolism)
  • Humans
  • Inflammation (complications, pathology)
  • Kidney (pathology)
  • Kidney Function Tests
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells (cytology, metabolism)
  • Neoplasms (pathology)
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury (complications, physiopathology)
  • Transduction, Genetic
  • Umbilical Cord (cytology)

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