J Korean Soc Pediatr Nephrol.  2010 Apr;14(1):32-41.

Mesenchymal Stem Cells Ameliorate Adriamycin Induced Proteinuric Nephropathy

Affiliations
  • 1Department of Pediatrics, Seoul National University Hospital, Seoul, Korea. ychoi@snu.ac.kr
  • 2Research Center for Rare Diseases, Seoul National University College of Medicine, Seoul, Korea.
  • 3Department of Pathology, Seoul National University Bundang Hospital, Bundang, Korea.
  • 4Kidney Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Abstract

PURPOSE
Glomerulonephropathy (GN) often manifests as proteinuria and progresses to chronic renal failure without specific therapy. Mesenchymal stem cell (MSC) has been tried as a therapeutic agent in experimental GN, and previous studies showed that administration of MSC concomitantly to the insult inducing GN or via intra-renal administration ameliorated proteinuria. The purpose of this study was to test the therapeutic potential of MSC administered via intravenous route at the time of clinically evident proteinuria.
METHODS
MSCs were administered intravenously via tail vain into the mice with adriamycin (ADR) induced nephropathy (ADR-GN), two weeks after ADR injection when massive proteinuria was evident. To test the capacity of MSC modulate the cytokine production in the inflammatory milieu, the concentrations of IFN-gamma and IL-10 were measured in the supernatant of in vitro mixed lymphocyte culture (MLC) with or without additional MSC.
RESULTS
MSCs administered intravenously into the proteinuric mice with ADR-GN accelerated the recovery of this experimental GN with disappearance of proteinuria in two weeks when the saline treated (control) mice still showed significant proteinuria. The mice treated with MSC also had a tendency of better survival. Addition of MSC decreased IFN-gamma and increased IL-10 in the supernatant of MLC.
CONCLUSION
This study showed that MSC had a therapeutic potential even when administered in a more clinically relevant setting into a proteinuric glomerulonephropathy model. Further study to verify the mechanism and long-term safety of this phenomenon is required.

Keyword

Glomerulonephropathy; Immune modulation; Mesenchymal stem cell; Proteinuria

MeSH Terms

Animals
Doxorubicin
Interleukin-10
Kidney Failure, Chronic
Lymphocytes
Mesenchymal Stromal Cells
Mice
Proteinuria
Doxorubicin
Interleukin-10
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