title: Human mesenchymal stem cells derived from adipose tissue reduce functional and tissue damage in a rat model of chronic renal failure.
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 0.5×10(6) 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.
authors.affiliation: Laboratory of Integrative and Molecular Physiology, Los Andes University, Santiago, Chile. svillanueva@uandes.cl
authors.forename: Sandra
authors.initials: S
authors.lastname: Villanueva
authors.forename: Juan E
authors.initials: JE
authors.lastname: Carreño
authors.forename: Lorena
authors.initials: L
authors.lastname: Salazar
authors.forename: César
authors.initials: C
authors.lastname: Vergara
authors.forename: Rocío
authors.initials: R
authors.lastname: Strodthoff
authors.forename: Francisca
authors.initials: F
authors.lastname: Fajre
authors.forename: Carlos
authors.initials: C
authors.lastname: Céspedes
authors.forename: Pablo J
authors.initials: PJ
authors.lastname: Sáez
authors.forename: Carlos
authors.initials: C
authors.lastname: Irarrázabal
authors.forename: Jorge
authors.initials: J
authors.lastname: Bartolucci
authors.forename: Fernando
authors.initials: F
authors.lastname: Figueroa
authors.forename: Carlos P
authors.initials: CP
authors.lastname: Vio
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D018919:Neovascularization, Physiologic; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D051762:PAX2 Transcription Factor / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015415:Biomarkers; D055419:Bone Morphogenetic Protein 7; D050814:Octamer Transcription Factor-3; D051762:PAX2 Transcription Factor; D042461:Vascular Endothelial Growth Factor A