V. Revol et al., A novel growth-factor-dependent myeloid cell line derived from mouse bone marrow cells contains progenitors endowed with high proliferative potential, EXP HEMATOL, 27(1), 1999, pp. 88-98
Constitutive expression of human colony-stimulating factor-1 receptor (CSF-
1R) confers long-lasting CSF-l-dependent proliferation to mouse myeloid cel
l lines, We developed mice transgenic for human CSF-1R because mouse CSF-I
cannot activate human CSF-IR, Then bone marrow cells from transgenic mice w
ere plated onto MS-5 stromal cells expressing the membrane form of human CS
F-I (2M-1 cells) in order to combine the hematopoietic supporting propertie
s of stromal cells and the proliferative effects of CSF-1, Thus, we were ab
le to derive a hematopoietic cell line, called 47.10, that grew indefinitel
y under these conditions, whereas no cell line could be developed front non
transgenic mice. Proliferation of 47.10 cells is severely affected by neutr
alizing anti-CSF-1R monoclonal antibodies. Morphologic and cytofluorometry
analysis established that most 47.10 cells are immature myelomonocytic cell
s. Consistent with this phenotype, the myeloid transcription factor PU.1, b
ut not the erythroid transcription factor GATA-1, is expressed in 47.10 cel
ls. A few 47.10 cells (3-5%) do not express lineage specific markers; they
differentiate spontaneously to lineage-positive cells after replating on 2M
-1 cells. In agar cultures, 47.10 cells form 7- and 14-day colonies in resp
onse to a cocktail of granulocyte/macrophage colony-stimulating factor (2.5
ng/mL), interleukin-3 (1 ng/mL), and mouse CSF-1 (10 ng/mL), Under these c
onditions, about 0.5% of 47.10 cells formed large 14-day colonies (>1 mm) c
omposed of mature monocytes and granulocytes, reflecting the presence of pr
ogenitors endowed with high proliferative potential (HPP-47.10 cells). In c
onclusion, we have characterized a novel continuous myeloid cell line prese
nting a hierarchical structure similar to that of the bone marrow progenito
r cell compartment, (C) 1999 International Society of Experimental Hematolo
gy. Published by Elsevier Science Inc.