Hematopoietic Stem Cells Contribute to the Regeneration of... : Journal of the American Society of Nephrology (original) (raw)

Molecular Medicine, Genetics and Development

Hematopoietic Stem Cells Contribute to the Regeneration of Renal Tubules after Renal Ischemia-Reperfusion Injury in Mice

Lin, Fangming*; Cordes, Kimberly*; Li, Linheng‡; Hood, Leroy§; Couser, William G.¶; Shankland, Stuart J.¶; Igarashi, Peter†

Departments of *Pediatrics and †Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas; ‡Stowers Institute for Medical Research, Kansas City, Missouri; §Institute for Systems Biology, Seattle, Washington; and ¶Department of Medicine, University of Washington, Seattle, Washington.

Correspondence to Dr. Fangming Lin, Division of Pediatric Nephrology, Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Mail Code 9063, Dallas, TX 75390-9063. Phone: 214-648-3438; Fax: 214-648-2034;

Accepted January 23, 2003

Received November 12, 2002

Journal of the American Society of Nephrology 14(5):p 1188-1199, May 2003. | DOI: 10.1097/01.ASN.0000061595.28546.A0

Abstract

ABSTRACT. Ischemia-reperfusion injury (I/R injury) is a common cause of acute renal failure. Recovery from I/R injury requires renal tubular regeneration. Hematopoietic stem cells (HSC) have been shown to be capable of differentiating into hepatocytes, cardiac myocytes, gastrointestinal epithelial cells, and vascular endothelial cells during tissue repair. The current study tested the hypothesis that murine HSC can contribute to the regeneration of renal tubular epithelial cells after I/R injury. HSC isolated from male Rosa26 mice that express β-galactosidase constitutively were transplanted into female nontransgenic mice after unilateral renal I/R injury. Four weeks after HSC transplantation, β-galactosidase-positive cells were detected in renal tubules of the recipients by X-Gal staining. PCR analysis of the male-specific Sry gene and Y chromosome fluorescence in situ hybridization confirmed the presence of male-derived cells in the kidneys of female recipients. Antibody co-staining showed that β-galactosidase was primarily expressed in renal proximal tubules. This is the first report to show that HSC can differentiate into renal tubular cells after I/R injury. Because of their availability, HSC may be useful for cell replacement therapy of acute renal failure. E-mail: [email protected]