Evaluation of the effect of autologous mesenchymal stem cell injection in a large-animal model of bilateral kidney ischaemia reperfusion injury.
OBJECTIVE
Adult mesenchymal stem cells (MSC) have been proven to be of benefit to the kidney in different experimental models of renal injuries. All studies have been performed in valuable rodent models, but the relevance of these results to large mammals and ultimately, to humans remains unknown. Therefore, the aim of this study was to investigate the effect of MSC transplantation in an alternative ovine large-animal model of bilateral kidney ischaemia reperfusion injury.


METHODS
Sheep were divided into three groups: one sham-operated group and two groups submitted to renal bilateral ischaemia for 60 min. Animals with ischaemia reperfusion injury were treated with injection of autologous MSCs or with vehicle medium.


RESULTS
The model sheep presented with renal histological manefestations that closely resembled lesions seen in patients. Transplanted MSCs were found in glomeruli but not in tubules and did not express glomerular cell markers (podocin, von Willebrand factor), but functional evaluation showed no beneficial effect of MSC infusion. Morphological and molecular analyses corroborated the functional results. MSCs did not repair kidney parenchyma and failed to modulate cell death and proliferation or cytokine release (tumour necrosis factor-alpha, vascular endothelial growth factor alpha (VEGF-alpha), Bcl-2, caspase).


CONCLUSIONS
In this unique autologous large-animal model, MSCs did not exhibit reparative or paracrine protective properties.
INSERM, U872, Centre de Recherche des Cordeliers, Paris, France. luc.behr@imm.fr
L
L
Behr
M
M
Hekmati
A
A
Lucchini
K
K
Houcinet
A-M
AM
Faussat
N
N
Borenstein
L-H
LH
Noel
M
M
Lelievre-Pegorier
K
K
Laborde
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D049109:Cell Proliferation; D017931:DNA Primers; D004195:Disease Models, Animal; D007668:Kidney / Q000098:blood supply*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D016133:Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000601:surgery*; D012756:Sheep; D033581:Stem Cell Transplantation
D017931:DNA Primers