Intra renal arterial injection of autologous mesenchymal stem cells in an ovine model in the postischemic kidney.
OBJECTIVE
Acute renal failure (ARF) remains a major healthcare problem. Although modern medical therapy has improved its outcome, the syndrome still has high mortality and morbidity rates [Xue et al.: J Am Soc Nephrol 2006;17:1135-1142]. Recently, stem cell (SC) therapies have been proposed as an alternative for the treatment of ARF on the basis of the damaged cells' replacement or enhanced recovery or regeneration. The aims of this study were to investigate the engraftment of autologous mesenchymal stem cells (MSC) injected into the renal artery in an ovine model of ischemia reperfusion injury (IRI) and to assess the consequence of the delay between injury and cell transplantation on the engraftment.


METHODS
MSC were transplanted in animals submitted to IRI or in healthy animals not submitted to IRI. Sheep with IRI were grafted at two different time points after injury. Unilateral renal IRI was performed by percutaneous transluminal placement of a balloon catheter in the renal artery. MSC were isolated from bone marrow, cultured, labeled and injected into the renal artery.


RESULTS
All ewes showed renal engraftment by MSC, both in tubules and glomeruli. MSC expressed tubular epithelial cell markers and podocyte phenotype. There was a significant increase of engraftment of tubules by MSC when cells were injected early after injury indicating that the delay for cell transplantation after ischemic insult should be short.


CONCLUSIONS
This is the first report of intra-arterial autologous transplantation of MSC in the kidney, resulting in a successful engraftment into tubular and glomerular structures. The results strongly suggest that the optimal time window for stem cell therapy is during the early phase of the ischemic injury.
Behr
Luc
L
INSERM, U872, Centre de Recherche des Cordeliers, Université Pierre et Marie Curie - Paris 6, UMR S872, Université Paris Descartes, UMR S872, Paris, France. luc.behr@imm.fr
Hekmati
Mehrak
M
Fromont
Gaëlle
G
Borenstein
Nicolas
N
Noel
Laure-Hélène
LH
Lelievre-Pegorier
Martine
M
Laborde
Kathleen
K
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D007269:Injections, Intra-Arterial; D007668:Kidney / Q000098:blood supply*; D007678:Kidney Glomerulus / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D050199:Podocytes / Q000378:metabolism; D012077:Renal Artery; D015427:Reperfusion Injury / Q000473:pathology / Q000601:surgery*; D012756:Sheep; D013997:Time Factors; D014182:Transplantation, Autologous
D015415:Biomarkers