Administered mesenchymal stem cells enhance recovery from ischemia/reperfusion-induced acute renal failure in rats
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Administered mesenchymal stem cells enhance recovery from ischemia/reperfusion-induced acute renal failure in rats. / Lange, Claudia; Tögel, Florian; Ittrich, Harald; Clayton, Frederic; Nolte-Ernsting, Claus; Zander, Axel R; Westenfelder, Christof.
in: KIDNEY INT, Jahrgang 68, Nr. 4, 01.10.2005, S. 1613-7.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Administered mesenchymal stem cells enhance recovery from ischemia/reperfusion-induced acute renal failure in rats
AU - Lange, Claudia
AU - Tögel, Florian
AU - Ittrich, Harald
AU - Clayton, Frederic
AU - Nolte-Ernsting, Claus
AU - Zander, Axel R
AU - Westenfelder, Christof
PY - 2005/10/1
Y1 - 2005/10/1
N2 - 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.CONCLUSION: 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.
AB - 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.CONCLUSION: 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.
KW - Acute Kidney Injury
KW - Animals
KW - Coloring Agents
KW - Ferrocyanides
KW - Graft Survival
KW - Iron-Dextran Complex
KW - Kidney
KW - Magnetic Resonance Imaging
KW - Male
KW - Mesoderm
KW - Rats
KW - Rats, Sprague-Dawley
KW - Recovery of Function
KW - Reperfusion Injury
KW - Stem Cell Transplantation
U2 - 10.1111/j.1523-1755.2005.00573.x
DO - 10.1111/j.1523-1755.2005.00573.x
M3 - SCORING: Journal article
C2 - 16164638
VL - 68
SP - 1613
EP - 1617
JO - KIDNEY INT
JF - KIDNEY INT
SN - 0085-2538
IS - 4
ER -