Human mesenchymal stem cells derived from adipose tissue reduce functional and tissue damage in a rat model of chronic renal failure

Sandra Villanueva, Juan E. Carreño, Lorena Salazar, César Vergara, Rocío Strodthoff, Francisca Fajre, Carlos Céspedes, Pablo J. Sáez, Carlos Ernesto Irarrazabal Muñoz, Jorge Bartolucci, Fernando Figueroa, Carlos P. Vio

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)199-210
Number of pages12
JournalClinical Science
Volume125
Issue number4
DOIs
StatePublished - Aug 2013

Keywords

  • Adipose-tissue-derived mesenchymal stem cell
  • Chronic kidney disease
  • Nephrectomy
  • Proteinuria
  • Renal functional recovery

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