Proliferation of human progenitor cells in a long-term culture system is more efficiently sustained by the addition of Flt-3 ligand or megakaryocyte growth and development factor than by Kit ligand.
BACKGROUND
We compared the effects of the early-acting growth factors (GF), Flt-3 ligand (FL), c-Kit ligand (KL), and leukemia inhibitory factor (LIF), and the late-acting GF, granulocyte-colony stimulating factor (G-CSF) and megakaryocyte growth and development factor (MGDF), added alone in human long-term marrow culture (LTMC).


METHODS
The GF were used in primary cultures of mononuclear cells (MNC) and in cocultures of CD34+ cells on murine preestablished MS-5 stromal layers. GF activity was assessed as nonadherent and adherent progenitor cell production and cobblestone area formation at week 5.


RESULTS
In this system, only FL, KL, and MGDF significantly stimulated early stages of hematopoiesis, whereas only G-CSF stimulated the proliferation of mature progenitor cells within the granulo-monocyte lineage and no effect was observed with LIF. FL displayed the strongest activity, and MGDF was more efficient than KL, both in primary cultures of MNC and in cocultures of CD34+ cells. However, the stimulatory effects of these GF used alone were dependent on the presence of a stromal layer.


CONCLUSIONS
These LTMC data emphasize the particular roles for FL and MGDF in the stimulation of primitive hematopoiesis.
Cartron
G
G
Laboratory of Hematology, CHRU Bretonneau, Tours, France.
Binet
C
C
Hérault
O
O
Cailliot
C
C
Bernard
M C
MC
Estienne
M H
MH
Clément
N
N
Colombat
Ph
P
Domenech
J
J
D000818:Animals; D018952:Antigens, CD34; D001854:Bone Marrow Cells / Q000166:cytology; D018929:Cell Culture Techniques / Q000379:methods; D002455:Cell Division / Q000187:drug effects; D018920:Coculture Techniques; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006131:Growth Inhibitors / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D019089:Stem Cell Factor / Q000494:pharmacology; D017154:Stromal Cells / Q000166:cytology; D013926:Thrombopoietin / Q000494:pharmacology; D013997:Time Factors
D018952:Antigens, CD34; D006131:Growth Inhibitors; D006133:Growth Substances; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D008565:Membrane Proteins; D019089:Stem Cell Factor; C084881:flt3 ligand protein; D016179:Granulocyte Colony-Stimulating Factor; D013926:Thrombopoietin