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Comparative effects of mesenchymal stem cell therapy in distinct stages of chronic renal failure
Heloisa Cristina Caldas1, Thaís Amarante Peres de Paula Couto1, Ida Maria Maximina Fernandes1
1Laboratory 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.
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.
Insights
Mesenchymal stem cell (MSC) therapy effectively slows chronic renal failure (CRF) progression in rats. Early intervention during less severe CRF stages shows greater therapeutic benefits for kidney function and morphology.
Area of Science:
- Regenerative Medicine
- Stem Cell Therapy
- Nephrology
Background:
- Adult stem cells, particularly mesenchymal stem cells (MSCs), show promise for treating chronic diseases.
- Chronic renal failure (CRF) is a progressive condition with limited therapeutic options.
- Investigating MSCs for retarding CRF progression in experimental models is crucial.
Purpose of the Study:
- To evaluate the efficacy of mesenchymal stem cell (MSC) therapy in retarding chronic renal failure (CRF) progression.
- To assess if MSC administration is more effective in less severe stages of CRF.
- To analyze the impact of MSC therapy on renal function and morphology in CRF models.
Main Methods:
- Two renal mass reduction models (5/6 and 2/3 reduction) were used to simulate CRF.
- Mesenchymal stem cells (MSCs) were isolated from bone marrow and administered to the remnant kidneys.
- Renal function (serum creatinine, creatinine clearance, proteinuria) and renal morphology were assessed.
Main Results:
- MSC therapy significantly reduced serum creatinine and proteinuria, increased creatinine clearance, and slowed its decline.
- Histological analysis revealed reduced glomerulosclerosis, tubulointerstitial fibrosis, and atrophy in MSC-treated rats.
- MSC treatment decreased inflammation, macrophage accumulation, and fibrosis markers; rats with less severe CRF (MSC2/3) showed better response.
Conclusions:
- Mesenchymal stem cell (MSC) therapy is effective in retarding the progression of chronic renal failure (CRF).
- MSC therapy appears to be more beneficial when administered during the earlier, less severe stages of CRF.
- MSC treatment offers a potential therapeutic strategy for managing CRF by improving renal function and structure.
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