Therapeutic effects of human mesenchymal stem cells in Wistar-Kyoto rats with anti-glomerular basement membrane glomerulonephritis.

Authors: Suzuki, T  Iyoda, M  Shibata, T  Ohtaki, H  Matsumoto, K  Shindo-Hirai, Y  Kuno, Y  Wada, Y  Yamamoto, Y  Kawaguchi, M  Shioda, S  Akizawa, T 
Citation: Suzuki T, etal., PLoS One. 2013 Jun 24;8(6):e67475. doi: 10.1371/journal.pone.0067475. Print 2013.
Pubmed: (View Article at PubMed) PMID:23826305
DOI: Full-text: DOI:10.1371/journal.pone.0067475

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, 3x10(6)) 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-alpha, IL-1beta, 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-beta 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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CRRD Object Information
CRRD ID: 7365004
Created: 2013-10-15
Species: All species
Last Modified: 2013-10-15
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.