Administration of Flk2/Flt3 ligand induces expansion of human high-proliferative potential colony-forming cells in the SCID-hu mouse.
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.
Namikawa
R
R
DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, CA, USA. rnamikawa@webjapan.com
Muench
M O
MO
Firpo
M T
MT
Humeau
L
L
Xu
Y
Y
Menon
S
S
Roncarolo
M G
MG
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D016025:Bone Transplantation; D001842:Bone and Bones / Q000196:embryology; D002455:Cell Division; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D016256:Lewis X Antigen / Q000032:analysis; D051379:Mice; D016513:Mice, SCID; D011518:Proto-Oncogene Proteins / Q000494:pharmacology*; D020794:Receptor Protein-Tyrosine Kinases / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D063268:Sialic Acid Binding Ig-like Lectin 3; D014183:Transplantation, Heterologous; D051941:fms-Like Tyrosine Kinase 3
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; C571165:Cd33 protein, mouse; D016256:Lewis X Antigen; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D063268:Sialic Acid Binding Ig-like Lectin 3; C497970:FLT3 protein, human; C497971:Flt3 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3