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Therapeutic Effects of Human Mesenchymal Stem Cells in Wistar-Kyoto Rats with Anti-Glomerular Basement Membrane Glomerulonephritis

Authors
Journal
PLoS ONE
1932-6203
Publisher
Public Library of Science
Publication Date
Volume
8
Issue
6
Identifiers
DOI: 10.1371/journal.pone.0067475
Keywords
  • Research Article
  • Biology
  • Developmental Biology
  • Stem Cells
  • Mesenchymal Stem Cells
  • Immunology
  • Immunopathology
  • Model Organisms
  • Animal Models
  • Rat
  • Molecular Cell Biology
  • Cellular Types
  • Medicine
  • Clinical Research Design
  • Animal Models Of Disease
  • Nephrology
  • Chronic Kidney Disease
Disciplines
  • Biology
  • Medicine

Abstract

Introduction Multipotent mesenchymal stem cells (MSCs) have become a promising therapeutic approach in many clinical conditions. The hypothesis that MSCs can provide a potential therapy for human anti-glomerular basement membrane (GBM) glomerulonephritis (GN) was tested. Methods Nephrotoxic serum nephritis was induced in Wistar-Kyoto rats on day 0. Groups of animals were given either human MSCs (hMSCs, 3×106) or vehicle by intravenous injection on day 4; all rats were sacrificed at either day 7 or day 13. Results Fluorescently labeled hMSCs were localized in glomeruli and tubulointerstitium 5 h after hMSC administration and persisted until 48 h, but hMSCs were barely detectable after 7 days. hMSC-treated rats had decreased kidney weight, proteinuria, and glomerular tuft area at each time point. The serum creatinine level and degree of glomerular crescent formation were decreased by hMSC treatment on day 13. ED1-positive macrophages, CD8-positive cells, and TUNEL-positive apoptotic cells in glomeruli were reduced by hMSC treatment on day 7, and this trend in apoptotic cells persisted to day 13. Renal cortical mRNA for TNF-α, IL-1β, and IL-17, and the serum IL-17A level were decreased, whereas renal cortical mRNA for IL-4 and Foxp3 and the serum IL-10 level were increased in the MSC-treated group on day 7. Collagen types I and III and TGF-β mRNA were decreased by hMSC treatment on day 13. Conclusion The present results demonstrated that anti-inflammatory and immunomodulatory effects were involved in the mechanism of attenuating established experimental anti-GBM GN by hMSCs. These results suggest that hMSCs are a promising therapeutic candidate for the treatment of anti-GBM GN.

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