Therapeutic approaches for CKD (chronic kidney disease) have been able to reduce proteinuria, but not diminish the disease progression. We have demonstrated beneficial effects by injection of BM (bone marrow)-derived MSCs (mesenchymal stem cells) from healthy donors in a rat model with CKD. However, it has recently been reported that BM-MSCs derived from uraemic patients failed to confer functional protection in a similar model. This suggests that autologous BM-MSCs are not suitable for the treatment of CKD. In the present study, we have explored the potential of MSCs derived from adipose tissue (AD-MSCs) as an alternative source of MSCs for the treatment of CKD. We have isolated AD-MSCs and evaluated their effect on the progression of CKD. Adult male SD (Sprague–Dawley) rats subjected to 5/6 NPX (nephrectomy) received a single intravenous infusion of 0.5×106 AD-MSCs or MSC culture medium alone. The therapeutic effect was evaluated by plasma creatinine measurement, structural analysis and angiogenic/epitheliogenic protein expression. AD-MSCs were detected in kidney tissues from NPX animals. This group had a significant reduction in plasma creatinine levels and a lower expression of damage markers ED-1 and α-SMA (α-smooth muscle actin) (P<0.05). In addition, treated rats exhibited a higher level of epitheliogenic [Pax-2 and BMP-7 (bone morphogenetic protein 7)] and angiogenic [VEGF (vascular endothelial growth factor)] proteins. The expression of these biomarkers of regeneration was significantly related to the improvement in renal function. Although many aspects of the cell therapy for CKD remain to be investigated, we provide evidence that AD-MSCs, a less invasive and highly available source of MSCs, exert an important therapeutic effect in this pathology.
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Research Article|
May 01 2013
Human mesenchymal stem cells derived from adipose tissue reduce functional and tissue damage in a rat model of chronic renal failure
Sandra Villanueva;
*Laboratory of Integrative and Molecular Physiology, Los Andes University, Santiago, Chile
Correspondence: Dr Sandra Villanueva (email [email protected]).
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Juan E. Carreño;
Juan E. Carreño
*Laboratory of Integrative and Molecular Physiology, Los Andes University, Santiago, Chile
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Lorena Salazar;
Lorena Salazar
†Cell Therapy Laboratory, Los Andes University, Santiago, Chile
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César Vergara;
César Vergara
*Laboratory of Integrative and Molecular Physiology, Los Andes University, Santiago, Chile
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Rocío Strodthoff;
Rocío Strodthoff
*Laboratory of Integrative and Molecular Physiology, Los Andes University, Santiago, Chile
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Francisca Fajre;
Francisca Fajre
*Laboratory of Integrative and Molecular Physiology, Los Andes University, Santiago, Chile
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Carlos Céspedes;
Carlos Céspedes
‡Department of Physiology, Center for Aging and Regeneration, Pontificia Universidad Católica de Chile, Santiago, Chile
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Pablo J. Sáez;
Pablo J. Sáez
‡Department of Physiology, Center for Aging and Regeneration, Pontificia Universidad Católica de Chile, Santiago, Chile
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Carlos Irarrázabal;
Carlos Irarrázabal
*Laboratory of Integrative and Molecular Physiology, Los Andes University, Santiago, Chile
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Jorge Bartolucci;
Jorge Bartolucci
†Cell Therapy Laboratory, Los Andes University, Santiago, Chile
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Fernando Figueroa;
Fernando Figueroa
†Cell Therapy Laboratory, Los Andes University, Santiago, Chile
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Carlos P. Vio
Carlos P. Vio
‡Department of Physiology, Center for Aging and Regeneration, Pontificia Universidad Católica de Chile, Santiago, Chile
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Publisher: Portland Press Ltd
Received:
November 30 2012
Revision Received:
March 05 2013
Accepted:
March 12 2013
Accepted Manuscript online:
March 12 2013
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2013 Biochemical Society
2013
Clin Sci (Lond) (2013) 125 (4): 199–210.
Article history
Received:
November 30 2012
Revision Received:
March 05 2013
Accepted:
March 12 2013
Accepted Manuscript online:
March 12 2013
Citation
Sandra Villanueva, Juan E. Carreño, Lorena Salazar, César Vergara, Rocío Strodthoff, Francisca Fajre, Carlos Céspedes, Pablo J. Sáez, Carlos Irarrázabal, Jorge Bartolucci, Fernando Figueroa, Carlos P. Vio; Human mesenchymal stem cells derived from adipose tissue reduce functional and tissue damage in a rat model of chronic renal failure. Clin Sci (Lond) 1 August 2013; 125 (4): 199–210. doi: https://doi.org/10.1042/CS20120644
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