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THE STEM CELL NICHE

Granulocyte Colony-Stimulating Factor Prior to Nonmyeloablative Irradiation Decreases Murine Host Hematopoietic Stem Cell Function and Increases Engraftment of Donor Marrow Cells

^aHerman B Wells Center for Pediatric Research, Department of Pediatrics, Sections of
^bNeonatal-Perinatal Medicine and
^dPediatric Hematology/Oncology, Riley Hospital for Children, and
Departments of ^cBiochemistry and Molecular Biology,
^eMicrobiology/Immunology, and
^fMedical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA

Key Words. Granulocyte colony-stimulating factor • Irradiation • Bone marrow transplant • Retrovirus • Gene therapy • Neutrophil

Correspondence: Mary C. Dinauer, M.D., Ph.D., Cancer Research Institute R4 402C, Indiana University School of Medicine, 1044 West Walnut Street, Indianapolis, Indiana 46202, USA. Telephone: 317-274-8645; Fax: 317-274-8679; e-mail: mdinauer{at}iupui.edu

Received on December 12, 2006; accepted for publication on February 27, 2007.

First published online in STEM CELLS EXPRESS  March 8, 2007.


The use of nonmyeloablative conditioning prior to bone marrow transplantation is an important component of transplantation-based therapies for nonmalignant blood diseases. In this study, treatment of recipient mice with granulocyte colony-stimulating factor (G-CSF) prior to low-dose total body irradiation (LD-TBI) enhanced long-term engraftment of freshly isolated congenic marrow 1.5- to 2-fold more than treatment with LD-TBI alone. This combined regimen was also evaluated in a mouse model of X-linked chronic granulomatous disease (X-CGD), where neutrophils have a defective NADPH oxidase due to genetic deletion of the gp91^phox subunit. Long-term engraftment of male X-CGD bone marrow cells cultured ex vivo for retroviral transduction of gp91^phox was enhanced by 40% when female X-CGD recipients were pretreated with G-CSF prior to 300 cGy. These data confirm that sequential treatment with G-CSF and LD-TBI prior to transplantation increases long-term engraftment of donor marrow, and they extend this approach to transplantation of murine donor marrow cultured ex vivo for gene transfer. Additional studies showed that the administration of G-CSF prior to LD-TBI did not alter early homing of donor marrow cells. However, the combined regimen significantly decreased the content of long-term repopulating cells in recipient marrow compared with LD-TBI alone, as assessed in competitive assays, which may contribute to the enhanced engraftment of donor marrow cells.

Disclosure of potential conflicts of interest is found at the end of this article.