title: Mesenchymal stem cell injection ameliorates chronic renal failure in a rat model.
abstract: CKD (chronic kidney disease) has become a public health problem. The therapeutic approaches have been able to reduce proteinuria, but have not been successful in limiting disease progression. In this setting, cell therapies associated with regenerative effects are attracting increasing interest. We evaluated the effect of MSC (mesenchymal stem cells) on the progression of CKD and the expression of molecular biomarkers associated with regenerative effects. Adult male Sprague-Dawley rats subjected to 5/6 NPX (nephrectomy) received a single intravenous infusion of 0.5×106 MSC or culture medium. A sham group subjected to the same injection was used as the control. Rats were killed 5 weeks after MSC infusion. Dye tracking of MSC was followed by immunofluorescence analysis. Kidney function was evaluated using plasma creatinine. Structural damage was evaluated by H&E (haematoxylin and eosin) staining, ED-1 abundance (macrophages) and interstitial α-SMA (α-smooth muscle actin). Repairing processes were evaluated by functional and structural analyses and angiogenic/epitheliogenic protein expression. MSC could be detected in kidney tissues from NPX animals treated with intravenous cell infusion. This group presented a marked reduction in plasma creatinine levels and damage markers ED-1 and α-SMA (P<0.05). In addition, treated rats exhibited a significant induction in epitheliogenic [Pax-2, bFGF (basic fibroblast growth factor) and BMP-7 (bone morphogenetic protein-7)] and angiogenic [VEGF (vascular endothelial growth factor) and Tie-2] proteins. The expression of these biomarkers of regeneration was significantly related to the increase in renal function. Many aspects of the cell therapy in CKD remain to be investigated in more detail: for example, its safety, low cost and the possible need for repeated cell injections over time. Beyond the undeniable importance of these issues, what still needs to be clarified is whether MSC administration has a real effect on the treatment of this pathology. It is precisely to this point that the present study aims to contribute.
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: Ernesto
authors.initials: E
authors.lastname: Ewertz
authors.forename: Flavio
authors.initials: F
authors.lastname: Carrión
authors.forename: Andrés
authors.initials: A
authors.lastname: Tapia
authors.forename: César
authors.initials: C
authors.lastname: Vergara
authors.forename: Carlos
authors.initials: C
authors.lastname: Céspedes
authors.forename: Pablo J
authors.initials: PJ
authors.lastname: Sáez
authors.forename: Patricia
authors.initials: P
authors.lastname: Luz
authors.forename: Carlos
authors.initials: C
authors.lastname: Irarrázabal
authors.forename: Juan E
authors.initials: JE
authors.lastname: Carreño
authors.forename: Fernando
authors.initials: F
authors.lastname: Figueroa
authors.forename: Carlos P
authors.initials: CP
authors.lastname: Vio
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism; D004195:Disease Models, Animal; D005346:Fibroblast Growth Factors / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000502:physiology; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology; D051762:PAX2 Transcription Factor / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D042787:Receptor, TIE-2 / Q000378:metabolism; D012038:Regeneration / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D055419:Bone Morphogenetic Protein 7; D051762:PAX2 Transcription Factor; C551986:PAX2 protein, rat; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D005346:Fibroblast Growth Factors; D042787:Receptor, TIE-2