Mesenchymal Stem Cells Are Renotropic, Helping to Repair... : Journal of the American Society of Nephrology (original) (raw)

Pathophysiology of Renal Disease and Progression

Mesenchymal Stem Cells Are Renotropic, Helping to Repair the Kidney and Improve Function in Acute Renal Failure

Morigi, Marina*; Imberti, Barbara*; Zoja, Carla*; Corna, Daniela*; Tomasoni, Susanna*; Abbate, Mauro*; Rottoli, Daniela*; Angioletti, Stefania*; Benigni, Ariela*; Perico, Norberto*; Alison, Malcolm†; Remuzzi, Giuseppe*,‡

*Mario Negri Institute for Pharmacological Research, Bergamo, Italy; †Department of Histopathology, Imperial College London, Hammersmith Hospital, London, United Kingdom; and ‡Unit of Nephrology and Dialysis, Azienda Ospedaliera, Ospedali Riuniti di Bergamo, Bergamo, Italy

Correspondence to Dr. Marina Morigi, “Mario Negri” Institute for Pharmacological Research, Via Gavazzeni 11, 24125 Bergamo, Italy. Phone: +39-035-319-888; Fax: +39-035-319-331; E-mail: [email protected]

Accepted March 30, 2004

Received July 22, 2003

Journal of the American Society of Nephrology 15(7):p 1794-1804, July 2004. | DOI: 10.1097/01.ASN.0000128974.07460.34

Abstract

ABSTRACT. Injury to a target organ can be sensed by bone marrow stem cells that migrate to the site of damage, undergo differentiation, and promote structural and functional repair. This remarkable stem cell capacity prompted an investigation of the potential of mesenchymal and hematopoietic stem cells to cure acute renal failure. The model of renal injury induced in mice by the anticancer agent cisplatin was chosen. Injection of mesenchymal stem cells of male bone marrow origin remarkably protected cisplatin-treated syngeneic female mice from renal function impairment and severe tubular injury. Y chromosome–containing cells localized in the context of the tubular epithelial lining and displayed binding sites for Lens culinaris lectin, indicating that mesenchymal stem cells engraft the damaged kidney and differentiate into tubular epithelial cells, thereby restoring renal structure and function. Mesenchymal stem cells markedly accelerated tubular proliferation in response to cisplatin-induced damage, as revealed by higher numbers of Ki-67–positive cells within the tubuli with respect to cisplatin-treated mice that were given saline. Hematopoietic stem cells failed to exert beneficial effects. These results offer a strong case for exploring the possibility that mesenchymal stem cells by virtue of their renotropic property and tubular regenerative potential may have a role in the treatment of acute renal failure in humans.