Comparative effects of mesenchymal stem cell therapy in distinct stages of chronic renal failure

Background The therapeutic potential of adult stem cells in the treatment of chronic diseases is becoming increasingly evident. In the present study, we sought to assess whether treatment with mesenchymal stem cells (MSCs) efficiently retards progression of chronic renal failure (CRF) when administe...

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Published in:Clinical and experimental nephrology 2015-10, Vol.19 (5), p.783-789
Main Authors: Caldas, Heloisa Cristina, de Paula Couto, Thaís Amarante Peres, Fernandes, Ida Maria Maximina, Baptista, Maria Alice Sperto Ferreira, Kawasaki-Oyama, Rosa Sayoko, Goloni-Bertollo, Eny Maria, Braile, Domingo Marcolino, Abbud-Filho, Mario
Format: Article
Language:English
Subjects:
Actins - biosynthesis
Actins - genetics
Animals
Cell Proliferation
Creatinine - metabolism
Disease Progression
Female
Fibrosis - pathology
Glomerulosclerosis, Focal Segmental - pathology
Glomerulosclerosis, Focal Segmental - therapy
Kidney - pathology
Kidney Failure, Chronic - pathology
Kidney Failure, Chronic - therapy
Kidney Function Tests
Macrophages - pathology
Medicine
Medicine & Public Health
Mesenchymal Stem Cell Transplantation - methods
Mesenchymal Stromal Cells
Nephrology
Original Article
Proliferating Cell Nuclear Antigen - biosynthesis
Proliferating Cell Nuclear Antigen - genetics
Proteinuria - metabolism
Rats
Rats, Wistar
Urology
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Summary:Background The therapeutic potential of adult stem cells in the treatment of chronic diseases is becoming increasingly evident. In the present study, we sought to assess whether treatment with mesenchymal stem cells (MSCs) efficiently retards progression of chronic renal failure (CRF) when administered to experimental models of less severe CRF. Methods We used two renal mass reduction models to simulate different stages of CRF (5/6 or 2/3 mass renal reduction). Renal functional parameters measured were serum creatinine (SCr), creatinine clearance (CCr), rate of decline in CCr (RCCr), and 24-h proteinuria (PT24h). We also evaluated renal morphology by histology and immunohistochemistry. MSCs were obtained from bone marrow aspirates and injected into the renal parenchyma of the remnant kidneys of both groups of rats with CRF (MSC5/6 or MSC2/3). Results Animals from groups MSC5/6 and CRF2/3 seemed to benefit from MSC therapy because they showed significantly reduction in SCr and PT24h, increase in CCr and slowed the RCCr after 90 days. Treatment reduced glomerulosclerosis but significant improvement did occur in the tubulointerstitial compartment with much less fibrosis and atrophy. MSC therapy reduced inflammation by decreasing macrophage accumulation proliferative activity (PCNA-positive cells) and fibrosis (α-SM-actin). Comparisons of renal functional and morphological parameters responses between the two groups showed that rats MSC2/3 were more responsive to MSC therapy than MSC5/6. Conclusion This study showed that MSC therapy is efficient to retard CRF progression and might be more effective when administered during less severe stages of CRF.
ISSN:1342-1751
1437-7799
DOI:10.1007/s10157-015-1079-1