The effects of Flk2/Flt3 ligand (FL) administration on human hematopoiesis were investigated using SCID-hu mice transplanted with human fetal bone fragments. Treatment with recombinant human FL induced significant increases in the frequencies of the high-proliferative potential colony- forming cells and low-proliferative potential colony-forming cells in steady- state human bone marrow. FL also promoted the expansion of high-proliferative potential colony-forming cells and low-proliferative potential colony- forming cells in the human bone marrow during the recovery phase after irradiation, which was evident in increases in the frequencies as well as in the absolute numbers of colony-forming cells. Furthermore, higher percentages of CD33+CD15- cells were found in the marrows treated with FL as compared to that of controls, indicating that FL hastened the recovery of at least some aspect of myelopoiesis after irradiation. These results indicate that FL induces the expansion of primitive hematopoietic progenitor cells in vivo and, therefore, may be useful in treating patients to promote an early hematopoietic recovery after cytoablative therapies.
Bibliographical noteFunding Information:
We are grateful for the excellent technical assistance of Nicole Carballido-Perrig, Svetlana Antonenko, and the DNAX animal and FACS facilities. We also thank Dr. Jan E. de Vries for his support and encouragement throughout the project. DNAX Research Institute is supported by Schering-Plough Corporation.
Copyright 2007 Elsevier B.V., All rights reserved.
- Flk2/Flt3 ligand
- Hematopoietic progenitor cells
- SCID-hu mouse