Administered mesenchymal stem cells enhance recovery from ischemia/reperfusion-induced acute renal failure in rats.
BACKGROUND
Adult stem cells are promising for the development of novel therapies in regenerative medicine. Acute renal failure (ARF) remains a frequent clinical complication, associated with an unacceptably high mortality rate, in large part due to the ineffectiveness of currently available therapies. The aim of this study was, therefore, to evaluate the therapeutic effectiveness of bone marrow-derived mesenchymal stem cells in a rat model of ischemia/reperfusion (I/R) ARF.


METHODS
We used a common I/R model in rats to induce ARF by clamping both renal pedicles for 40 minutes. Mesenchymal stem cells were iron-dextran-labeled for in vivo tracking studies by magnetic resonance imaging (MRI) and kidneys were imaged for mesenchymal stem cells immediately after infusion and at day 3 after ARF. Renal injury was scored on day 3 and cells were additionally tracked by Prussian blue staining.


RESULTS
We show in I/R-induced ARF in rats, modeling the most common form of clinical ARF, that infusion of mesenchymal stem cells enhances recovery of renal function. Mesenchymal stem cells were found to be located in the kidney cortex after injection, as demonstrated by MRI. Mesenchymal stem cells-treated animals had both significantly better renal function on days 2 and 3 and better injury scores at day 3 after ARF. Histologically, mesenchymal stem cells were predominantly located in glomerular capillaries, while tubules showed no iron labeling, indicating absent tubular transdifferentiation.


CONCLUSIONS
We conclude that the highly renoprotective capacity of mesenchymal stem cells opens the possibility for a cell-based paradigm shift in the treatment of I/R ARF.
Lange
Claudia
C
Department of Bone Marrow Transplantation, University of Hamburg, Hamburg, Germany.
Tögel
Florian
F
Ittrich
Harald
H
Clayton
Frederic
F
Nolte-Ernsting
Claus
C
Zander
Axel R
AR
Westenfelder
Christof
C
D058186:Acute Kidney Injury / Q000473:pathology / Q000628:therapy*; D000818:Animals; D004396:Coloring Agents; D005295:Ferrocyanides; D006085:Graft Survival; D007505:Iron-Dextran Complex; D007668:Kidney / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008648:Mesoderm / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D015427:Reperfusion Injury / Q000473:pathology / Q000628:therapy*; D033581:Stem Cell Transplantation
D004396:Coloring Agents; D005295:Ferrocyanides; D007505:Iron-Dextran Complex; C000170:ferric ferrocyanide