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Published ahead of print on April 6, 2005
J Am Soc Nephrol 16: 1723-1732, 2005
© 2005 American Society of Nephrology
doi: 10.1681/ASN.2004121089

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Pathophysiology of Renal Disease and Progression

Proliferation of Bone Marrow-Derived Cells Contributes to Regeneration after Folic Acid-Induced Acute Tubular Injury

Te-Chao Fang*,{dagger},{ddagger}, Malcolm R. Alison*,{dagger}, H. Terence Cook§, Rosemary Jeffery*, Nicholas A. Wright*,{dagger} and Richard Poulsom*,{dagger}

* Histopathology Unit, Cancer Research UK, London, United Kingdom; {dagger} Institute of Cell and Molecular Science, Queen Mary’s School of Medicine and Dentistry, University of London, United Kingdom; {ddagger} Division of Nephrology, Tzu Chi General Hospital, Hualien, Taiwan; and § Division of Investigative Science, Imperial College, University of London, London, United Kingdom

Address correspondence to: Prof. Richard Poulsom, Histopathology Unit, Cancer Research UK, London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3PX, UK. Phone: +44-20-7269-3438; Fax: +44-20-7269-3491; E-mail: richard.poulsom{at}cancer.org.uk

Received for publication December 15, 2004. Accepted for publication February 28, 2005.

Studies of tissue from recipients of bone marrow transplantation or organ allograft suggest that bone marrow-derived cells (BMDC) may differentiate into a variety of nonhematologic tissues, including renal tubular epithelium. The aims of this study were to examine whether BMDC contribute to recovery after acute renal injury and to assess the effects of cytokine mobilization on regeneration. Female mice (6 wk old) were lethally irradiated and transplanted with male bone marrow (BM) cells and later assigned into control, folic acid-treatment, and folic acid-treatment with granulocyte-colony stimulating factor (G-CSF), and control with G-CSF. Tritiated thymidine was given 1 h before death. Kidney sections were stained for a tubular epithelial marker, Y chromosome (in situ hybridization), periodic acid-Schiff staining, and subjected to autoradiography. Renal tubular epithelial cells in S-phase were scored as female (indigenous) or male (BM-derived). This is the first report to show that BMDC can respond by engrafting the renal tubules and undergo DNA synthesis after acute renal injury. BMDC contributed to the renal tubular epithelial cell population, although most (90%) renal tubular regeneration came from female indigenous cells. Some evidence was found for cell fusion between indigenous renal tubular cells and BMDC, but this was infrequent and the significance and consequences of cell fusion in the kidney are unresolved. G-CSF treatment nearly doubled the frequency of thymidine-labeled BM-derived tubular cells and might facilitate the recovery of renal tubular epithelium.




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