Poor cell survival limits the beneficial impact of mesenchymal stem cell transplantation on acute kidney injury.
BACKGROUND
Although renal tubular epithelium has a great capacity for repair it has been suggested that the administration of mesenchymal stem cells may accelerate the recovery following severe ischemic injury.


METHODS
Here we analyzed the survival rate and organ distribution of transplanted mesenchymal stem cells as well as their contribution to kidney regeneration after ischemic renal injury using functional tests, histological examination as well as quantitative real-time PCR.


RESULTS
Intravenously injected stem cells were mainly trapped in lungs and liver. One hour after injection, less than 1% of the injected stem cells could be detected in the injured kidneys. These cells disappeared within the first few days and did not replace renal epithelial cells precluding substantial transdifferentiation. To clarify whether reinforced stem cell delivery might promote sustained survival or conversion to tubular epithelia, stem cells were directly injected into the injured kidneys. Although these grafted cells also did not show sustained survival or contribute to structural renal repair, stem cell injection was associated with a significant but transient initial decrease in serum creatinine.


CONCLUSIONS
These data suggest that mesenchymal stem cells do not significantly contribute to epithelial renewal after ischemic injury, promoting the idea that the major impact of cell-based therapy for acute kidney injury may result from paracrine or endocrine effects unrelated to stem cell transdifferentiation.
Burst
Volker R
VR
Renal Division, Department of Medicine, University of Cologne, Cologne, Germany. volker.burst@uk-koeln.de
Gillis
Meyke
M
Pütsch
Florian
F
Herzog
Ruth
R
Fischer
Jürgen H
JH
Heid
Petra
P
Müller-Ehmsen
Jochen
J
Schenk
Kerstin
K
Fries
Jochen W U
JW
Baldamus
Conrad A
CA
Benzing
Thomas
T
D058186:Acute Kidney Injury / Q000209:etiology / Q000628:therapy*; D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival; D005260:Female; D007668:Kidney / Q000098:blood supply / Q000473:pathology*; D008099:Liver / Q000166:cytology; D008168:Lung / Q000166:cytology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051381:Rats; D011916:Rats, Inbred F344; D012038:Regeneration; D015427:Reperfusion Injury / Q000150:complications