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Isolation and Characterization of Kidney-Derived Stem Cells

Sandeep Gupta^*,, Catherine Verfaillie^*,, David Chmielewski^*, Stefan Kren^*, Keith Eidman^*, Jeffrey Connaire^*, Yves Heremans, Troy Lund, Mark Blackstad, Yuehua Jiang, Aernout Luttun and Mark E. Rosenberg^*

^* Department of Medicine and Stem Cell Institute, University of Minnesota, and Veterans Affairs Medical Center, Minneapolis, Minnesota

Address correspondence to: Dr. Sandeep Gupta, Division of Renal Diseases and Hypertension, Department of Medicine, University of Minnesota, 516 Delaware Street SE, Box 736, Minneapolis, MN 55455. Phone: 612-624-9444; Fax: 612-626-3840; E-mail: gupta024{at}umn.edu

Received for publication March 24, 2006. Accepted for publication August 7, 2006.

Acute kidney injury is followed by regeneration of damaged renal tubular epithelial cells. The purpose of this study was to test the hypothesis that renal stem cells exist in the adult kidney and participate in the repair process. A unique population of cells that behave in a manner that is consistent with a renal stem cell were isolated from rat kidneys and were termed multipotent renal progenitor cells (MRPC). Features of these cells include spindle-shaped morphology; self-renewal for >200 population doublings without evidence for senescence; normal karyotype and DNA analysis; and expression of vimentin, CD90 (thy1.1), Pax-2, and Oct4 but not cytokeratin, MHC class I or II, or other markers of more differentiated cells. MRPC exhibit plasticity that is demonstrated by the ability of the cells to be induced to express endothelial, hepatocyte, and neural markers by reverse transcriptase–PCR and immunohistochemistry. The cells can differentiate into renal tubules when injected under the capsule of an uninjured kidney or intra-arterially after renal ischemia-reperfusion injury. Oct4 expression was seen in some tubular cells in the adult kidney, suggesting these cells may be candidate renal stem cells. It is proposed that MRPC participate in the regenerative response of the kidney to acute injury.

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