Heloisa Cristina Caldas1, Thaís Amarante Peres de Paula Couto1, Ida Maria Maximina Fernandes1, Maria Alice Sperto Ferreira Baptista1, Rosa Sayoko Kawasaki-Oyama1,2, Eny Maria Goloni-Bertollo2, Domingo Marcolino Braile1, Mario Abbud-Filho3,4,5. 1. Laboratory of Immunology and Experimental Transplantation-LITEX, Department of Medicine/Nephrology, Medical School, FAMERP-HB/FUNFARME, Av Brigadeiro Faria Lima 5416, Sao Jose do Rio Preto, SP, 15090-000, Brazil. 2. Genetics and Molecular Biology Research Unit Laboratory-UPGEM, Department of Medicine/Nephrology, Medical School, FAMERP-HB/FUNFARME, Sao Jose do Rio Preto, SP, Brazil. 3. Laboratory of Immunology and Experimental Transplantation-LITEX, Department of Medicine/Nephrology, Medical School, FAMERP-HB/FUNFARME, Av Brigadeiro Faria Lima 5416, Sao Jose do Rio Preto, SP, 15090-000, Brazil. mabbud@terra.com.br. 4. Genetics and Molecular Biology Research Unit Laboratory-UPGEM, Department of Medicine/Nephrology, Medical School, FAMERP-HB/FUNFARME, Sao Jose do Rio Preto, SP, Brazil. mabbud@terra.com.br. 5. Instituto de Urologia e Nefrologia, Sao Jose do Rio Preto, SP, Brazil. mabbud@terra.com.br.
Abstract
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.
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.
Authors: H C Caldas; I M M Fernandes; F Gerbi; A C Souza; M A S F Baptista; H J Ramalho; R S Kawasaki-Oyama; E M Goloni-Bertollo; E C Pavarino-Bertelli; D M Braile; M Abbud-Filho Journal: Transplant Proc Date: 2008-04 Impact factor: 1.066
Authors: Regina Vogelbacher; Sandra Wittmann; Andrea Braun; Christoph Daniel; Christian Hugo Journal: Transplantation Date: 2007-12-15 Impact factor: 4.939
Authors: Heloisa Cristina Caldas; Fernando Henrique Lojudice; Cinthia Dias; Ida Maria Maximina Fernandes-Charpiot; Maria Alice Sperto Ferreira Baptista; Rosa Sayoko Kawasaki-Oyama; Mari Cleide Sogayar; Christina Maeda Takiya; Mario Abbud-Filho Journal: Stem Cells Int Date: 2017-08-03 Impact factor: 5.443