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Anemia
Volume 2010, Article ID 947816, 13 pages
http://dx.doi.org/10.1155/2010/947816
Research Article

Correction of Fanconi Anemia Group C Hematopoietic Stem Cells Following Intrafemoral Gene Transfer

Unité de Recherche en Pédiatrie, Department of Pediatrics, Université Laval, CHUQ-CHUL, RC-9800, 2705 Boulevard Laurier, Québec, QC, Canada G1V 4G2

Received 1 October 2009; Accepted 17 December 2009

Academic Editor: Maureen E. Hoatlin

Copyright © 2010 Ouassila Habi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The main cause of morbidity and mortality in Fanconi anemia patients is the development of bone marrow (BM) failure; thus correction of hematopoietic stem cells (HSCs) through gene transfer approaches would benefit FA patients. However, gene therapy trials for FA patients using ex vivo transduction protocols have failed to provide long-term correction. In addition, ex vivo cultures have been found to be hazardous for FA cells. To circumvent negative effects of ex vivo culture in FA stem cells, we tested the corrective ability of direct injection of recombinant lentiviral particles encoding FancC-EGFP into femurs of mice. Using this approach, we show that HSCs were efficiently corrected. Intrafemoral gene transfer of the gene prevented the mitomycin C-induced BM failure. Moreover, we show that intrafemoral gene delivery into aplastic marrow restored the bone marrow cellularity and corrected the remaining HSCs. These results provide evidence that targeting FA-deficient HSCs directly in their environment enables efficient and long-term correction of BM defects in FA.