Journal Article

Human cord blood CD133<sup>+</sup> cells exacerbate ischemic acute kidney injury in mice

Dylan Burger, Alex Gutsol, Anthony Carter, David S. Allan, Rhian M. Touyz and Kevin D. Burns

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 27, issue 10, pages 3781-3789
Published in print October 2012 | ISSN: 0931-0509
Published online May 2012 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfs110
Human cord blood CD133+ cells exacerbate ischemic acute kidney injury in mice

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Background

Acute kidney injury (AKI) in humans has few therapeutic options. In experimental models, administration of progenitor cells facilitates recovery from AKI. Human umbilical cord-derived CD133+ progenitor cells promote endothelial repair in ischemic limb, heart and brain tissue.

Methods

We examined the effects of human CD133+ progenitor cells in bilateral ischemia–reperfusion (I/R) kidney injury in non-obese diabetic severe combined immunodeficient mice. CD133+ cells from human cord blood were injected intravenously at the time of reperfusion and the extent of injury was determined by plasma biochemistry and kidney histology.

Results

In mice with I/R, fluorescently labeled CD133+ cells were detected in blood 2 min after injection but decreased rapidly thereafter with no evidence of homing to the kidneys. In mice subjected to I/R, CD133+ cells significantly increased plasma urea and Cr at 24 h compared to vehicle- or CD133 cell-treated mice. CD133+ cells exacerbated tubular necrosis and apoptosis, increased plasma tumor necrosis factor-α and increased kidney neutrophil infiltration. In contrast, CD133+ cells did not affect tubular cell proliferation. Administration of CD133+ cells to FVB/N mice post-I/R also augmented kidney injury.

Conclusions

These data indicate that human cord blood-derived CD133+ cells unexpectedly exacerbate ischemic AKI in mice, possibly through soluble factors. Our study highlights the importance of caution in cell-based therapies for human AKI.

Keywords: acute kidney injury; apoptosis; inflammation; ischemia–reperfusion; stem cells

Journal Article.  4471 words.  Illustrated.

Subjects: Nephrology

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