Mesenchymal Stem Cells Ameliorate Adriamycin Induced Proteinuric Nephropathy

Kang, Hee-Gyung; Park, So-Yeon; Ha, Il-Soo; Cheong, Hae-Il; Choi, Yong

doi:2010.14.1.32

J Korean Soc Pediatr Nephrol > Volume 14(1); 2010 > Article

J Korean Soc Pediatr Nephrol 2010;14(1): 32-41. doi: https://doi.org/10.3339/jkspn.2010.14.1.32

Adriamycin 유발 신병증에서 중간엽 줄기세포의 완화 효과

강희경, 박소연, 하일수, 정해일, 최용

¹서울대학교 의과대학 소아과학교실
²서울대학교 의과대학 병리학교실
³서울대학교 의과대학 소아과학교실
⁴서울대학교 의과대학 소아과학교실
⁵서울대학교 의과대학 소아과학교실

Mesenchymal Stem Cells Ameliorate Adriamycin Induced Proteinuric Nephropathy

Hee-Gyung Kang, So-Yeon Park, Il-Soo Ha, Hae-Il Cheong, Yong Choi

¹Department of Pediatrics, Seoul National University Hospital
²Department of Pathology, Seoul National University College of Medicine
³Department of Pediatrics, Seoul National University Hospital
⁴Department of Pediatrics, Seoul National University Hospital
⁵Department of Pediatrics, Seoul National University Hospital

Received: March 26, 2010; Revised: March 31, 2010. Accepted: April 13, 2010.

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.

Key words: Glomerulonephropathy | Immune modulation | Mesenchymal stem cell | Proteinuria