Skip to main content
SpringerLink
Log in

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

  • Original Article
  • Published:
Clinical and Experimental Nephrology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Romagnani P, Kalluri R. Possible mechanisms of kidney repair. Fibrogenesis. Tissue Repair. 2009;26:1–10.

    Google Scholar 

  2. Caldas HC, Fernandes IM, Gerbi F, Souza AC, Baptista MA, Ramalho HJ, Kawasaki-Oyama RS, Goloni-Bertollo EM, Pavarino-Bertelli EC, Braile DM, Abbud-Filho M. Effect of whole bone marrow cell infusion in the progression of experimental chronic renal failure. Transplant Proc. 2008;40:853–5.

    Article  CAS  PubMed  Google Scholar 

  3. Cavaglieri RC, Martini D, Sogayar MC, Noronha IL. Mesenchymal stem cells delivered at the subcapsule of the kidney ameliorate renal disease in the rat remnant kidney model. Transplant Proc. 2009;41:947–51.

    Article  CAS  PubMed  Google Scholar 

  4. Roessger A, Denk L, Minuth WW. Potential of stem/progenitor cell cultures within polyester fleeces to regenerate renal tubules. Biomaterials. 2009;30:3723–855.

    Article  CAS  PubMed  Google Scholar 

  5. Semedo P, Correa-Costa M, Cenedeze MA, Malheiros DM, Reis MA, Shimizu MH, Seguro AC, Pacheco-Silva A, Saraiva Camara NO. Mesenchymal stem cells attenuate renal fibrosis through immune modulation and remodeling properties in a rat remnant kidney model. Stem Cells. 2009;27:3063–73.

    CAS  PubMed  Google Scholar 

  6. Alexandre CS, Volpini RA, Shimizu MH, Sanches TR, Semedo P, Jura DIVL, Câmara NO, Seguro AC, Andrade L. Lineage-negative bone marrow cells protect against chronic renal failure. Stem Cells. 2009;27:682–92.

    Article  CAS  PubMed  Google Scholar 

  7. Choi S, Park M, Kim J, Hwang S, Park S, Lee Y. The role of mesenchymal stem cells in the functional improvement of chronic renal failure. Stem Cells Dev. 2009;18:521–9.

    Article  CAS  PubMed  Google Scholar 

  8. Gabizon D, Goren E, Shaked U, Averbukh Z, Rosenmann E, Modai D. Induction of chronic renal failure in the mouse: a new model. Nephron. 1985;40:349–52.

    Article  CAS  PubMed  Google Scholar 

  9. Szabo AJ, Muller V, Chen GF, Samsell LJ, Erdely A, Baylis C. Nephron number determines susceptibility to renal mass reduction-induced CRF in Lewis and Fisher 344 rats: implications for development of experimentally induced chronic allograft nephropathy. Nephron Dial Transplant. 2008;23:2492–5.

    Article  Google Scholar 

  10. Hishikawa K, Fujita T. Stem cells and kidney disease. Hypertens Res. 2006;29:745–9.

    Article  CAS  PubMed  Google Scholar 

  11. Hostetter TH. Progression of renal disease and renal hypertrophy. Annu Rev Physiol. 1995;57:263–78.

    Article  CAS  PubMed  Google Scholar 

  12. Caldas HC, Fernandes IM, Kawasaki-Oyama RS, Baptista MA, Plepis AM, Martins VA, Coimbra TM, Goloni-Bertollo EM, Braile DM, Abbud-Filho M. Effect of stem cells seeded onto biomaterial on the progression of experimental chronic kidney disease. Exp Biol Med. 2011;236:746–54.

    Article  CAS  Google Scholar 

  13. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, SimonettI DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;5411:143–7.

    Article  Google Scholar 

  14. Vogelbacher R, Wittmann S, Braun A, Daniel C, Hugo C. The mTOR inhibitor everolimus induces proteinuria and renal deterioration in the remnant kidney model in the rat. Transplantation. 2007;84:1492–9.

    Article  CAS  PubMed  Google Scholar 

  15. Veniant M, Heudes D, Clozel JP, Bruneval P, Menard J. Calcium blockade versus ACE inhibition in clipped and unclipped kidneys of 2K-1C rats. Kidney Int. 1994;46:421–9.

    Article  CAS  PubMed  Google Scholar 

  16. Curtis JJ, Rakowski TA, Argy WP Jr, Schreiner GE. Evaluation of percutaneous kidney biopsy in advanced renal failure. Nephron. 1976;17:259–69.

    Article  CAS  PubMed  Google Scholar 

  17. Coimbra TM, Janssen U, Grone HJ, Ostendorf T, Kunter U, Schmidt H, Brabant G, Floege J. Early events leading to renal injury in obese Zucker (fatty) rats with type II diabetes. Kidney Int. 2000;57:167–82.

    Article  CAS  PubMed  Google Scholar 

  18. Remuzzi A, Gagliardini E, Sangalli F, Bonomelli M, Piccinelli M, Benigni A, Remuzzi G. ACE inhibition reduces glomerulosclerosis and regenerates glomerular tissue in a model of progressive renal disease. Kidney Int. 2006;69:1124–30.

    Article  CAS  PubMed  Google Scholar 

  19. Walker MR, Patel KK, Stappenbeck TS. The stem cell niche. J Pathol. 2009;217:169.

    Article  CAS  PubMed  Google Scholar 

  20. Herrera MB, Bussolati B, Bruno S, Fonsato V, Romanazzi GM, Camussi G, Fonsato V, Romanazzi GM, Camussi G. Mesenchymal stem cells contribute to the renal repair of acute tubular epithelial injury. Int J Mol Med. 2004;14:1035–41.

    PubMed  Google Scholar 

  21. Morigi M, Imberti B, Zoja C, Corna D, TomasonI S, Abbate M, Rottoli D, Angioletti S, Benigni A, Perico N, AlisoN M, Remuzzi G. Mesenchymal stem cells are renotropic, helping to repair the kidney and improve function in acute renal failure. J Am Soc Nephrol. 2004;15:1794–804.

    Article  PubMed  Google Scholar 

  22. Duffield JS, Bonventre JV. Kidney tubular epithelium is restored without replacement with bone marrow-derived cells during repair after ischemic injury. Kidney Int. 2005;68:1956–61.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Coordination of Improvement of Higher Education Personnel (CAPES) and FAMERP/FUNFARME.

Conflict of interest

All the authors declared no competing interests.

Author information

Authors and Affiliations

  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

    Heloisa Cristina Caldas, Thaís Amarante Peres de Paula Couto, Ida Maria Maximina Fernandes, Maria Alice Sperto Ferreira Baptista, Rosa Sayoko Kawasaki-Oyama, Domingo Marcolino Braile & Mario Abbud-Filho

  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

    Rosa Sayoko Kawasaki-Oyama, Eny Maria Goloni-Bertollo & Mario Abbud-Filho

  3. Instituto de Urologia e Nefrologia, Sao Jose do Rio Preto, SP, Brazil

    Mario Abbud-Filho

Authors
  1. Heloisa Cristina Caldas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thaís Amarante Peres de Paula Couto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ida Maria Maximina Fernandes
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria Alice Sperto Ferreira Baptista
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rosa Sayoko Kawasaki-Oyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eny Maria Goloni-Bertollo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Domingo Marcolino Braile
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mario Abbud-Filho
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mario Abbud-Filho.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Caldas, H.C., de Paula Couto, T.A.P., Fernandes, I.M.M. et al. Comparative effects of mesenchymal stem cell therapy in distinct stages of chronic renal failure. Clin Exp Nephrol 19, 783–789 (2015). https://doi.org/10.1007/s10157-015-1079-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10157-015-1079-1

Keywords

Search

Navigation