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Effect of flt3 ligand on in vitro growth and expansion of colony-forming bone marrow cells from patients with aplastic anemia.
Exp Hematol. 1997 Jul; 25(7):573-81.EH

Abstract

To determine the value of flt3 ligand (flt3L) in stimulating hematopoiesis in human hypoproliferative bone marrow disorders, we examined its in vitro effect on bone marrow cells from patients with aplastic anemia (AA). Growth response to flt3L, alone and in combination with other hematopoietic growth factors, was investigated in clonogenic methylcellulose assays, in long-term liquid and stroma cultures. Bone marrow cells were derived from 13 AA patients with persisting in vitro growth defect after immunosuppressive treatment and from nine normal bone marrow donors. In methylcellulose cultures, flt3L stimulated formation of hematopoietic colonies only weakly, whereas it had an additive effect when combined with erythropoietin (Epo), stem cell factor (SCF), interleukin-3 (IL-3), interleukin-11 (IL-11), or granulocyte colony-stimulating factor (G-CSF). Flt3L was less effective than SCF and did not further enhance the number of hematopoietic colonies formed in response to SCF-containing combinations of multiple cytokines. In long-term liquid suspension cultures, flt3L was less mitogenic than SCF but its effect on the maintenance of progenitors was superior that of SCF and of IL-3, IL-11, and G-CSF. The total number of clonogenic AA cells increased as much as four-fold during the first culture week and FACS analysis demonstrated expansion of the CD34+CD38+ progenitor cell subset. Despite this enhancement, survival of AA cells remained significantly poorer than that of normal cells, in which the primitive subset of CD34+CD38- cells was maintained up to 4 weeks when flt3L was used as a single factor. Both in normal and AA cultures, flt3L promoted differentiation of cells of the myeloid lineages. In cultures of bone marrow stroma, flt3L had almost no effect on growth and survival of AA progenitors, while in cultures of normal cells the number of colony-forming cells increased up to 10-fold. Although flt3L does not overcome the proliferative defect of AA precursors, we conclude that the ligand is capable of in vitro stimulation and expansion of the reduced progenitor cell pool in AA, when used in appropriate culture conditions. The in vitro effects of flt3L on AA cells differ in many aspects from those of the structurally related cytokine SCF, suggesting a benefit in use of a combination of these two early-acting growth factors.

Authors+Show Affiliations

Department of Research, University Hospital Basel, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

9216732

Citation

Wodnar-Filipowicz, A, et al. "Effect of Flt3 Ligand On in Vitro Growth and Expansion of Colony-forming Bone Marrow Cells From Patients With Aplastic Anemia." Experimental Hematology, vol. 25, no. 7, 1997, pp. 573-81.
Wodnar-Filipowicz A, Chklovskaia E, Manz CY, et al. Effect of flt3 ligand on in vitro growth and expansion of colony-forming bone marrow cells from patients with aplastic anemia. Exp Hematol. 1997;25(7):573-81.
Wodnar-Filipowicz, A., Chklovskaia, E., Manz, C. Y., Lyman, S. D., & Nissen, C. (1997). Effect of flt3 ligand on in vitro growth and expansion of colony-forming bone marrow cells from patients with aplastic anemia. Experimental Hematology, 25(7), 573-81.
Wodnar-Filipowicz A, et al. Effect of Flt3 Ligand On in Vitro Growth and Expansion of Colony-forming Bone Marrow Cells From Patients With Aplastic Anemia. Exp Hematol. 1997;25(7):573-81. PubMed PMID: 9216732.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of flt3 ligand on in vitro growth and expansion of colony-forming bone marrow cells from patients with aplastic anemia. AU - Wodnar-Filipowicz,A, AU - Chklovskaia,E, AU - Manz,C Y, AU - Lyman,S D, AU - Nissen,C, PY - 1997/7/1/pubmed PY - 1997/7/1/medline PY - 1997/7/1/entrez SP - 573 EP - 81 JF - Experimental hematology JO - Exp Hematol VL - 25 IS - 7 N2 - To determine the value of flt3 ligand (flt3L) in stimulating hematopoiesis in human hypoproliferative bone marrow disorders, we examined its in vitro effect on bone marrow cells from patients with aplastic anemia (AA). Growth response to flt3L, alone and in combination with other hematopoietic growth factors, was investigated in clonogenic methylcellulose assays, in long-term liquid and stroma cultures. Bone marrow cells were derived from 13 AA patients with persisting in vitro growth defect after immunosuppressive treatment and from nine normal bone marrow donors. In methylcellulose cultures, flt3L stimulated formation of hematopoietic colonies only weakly, whereas it had an additive effect when combined with erythropoietin (Epo), stem cell factor (SCF), interleukin-3 (IL-3), interleukin-11 (IL-11), or granulocyte colony-stimulating factor (G-CSF). Flt3L was less effective than SCF and did not further enhance the number of hematopoietic colonies formed in response to SCF-containing combinations of multiple cytokines. In long-term liquid suspension cultures, flt3L was less mitogenic than SCF but its effect on the maintenance of progenitors was superior that of SCF and of IL-3, IL-11, and G-CSF. The total number of clonogenic AA cells increased as much as four-fold during the first culture week and FACS analysis demonstrated expansion of the CD34+CD38+ progenitor cell subset. Despite this enhancement, survival of AA cells remained significantly poorer than that of normal cells, in which the primitive subset of CD34+CD38- cells was maintained up to 4 weeks when flt3L was used as a single factor. Both in normal and AA cultures, flt3L promoted differentiation of cells of the myeloid lineages. In cultures of bone marrow stroma, flt3L had almost no effect on growth and survival of AA progenitors, while in cultures of normal cells the number of colony-forming cells increased up to 10-fold. Although flt3L does not overcome the proliferative defect of AA precursors, we conclude that the ligand is capable of in vitro stimulation and expansion of the reduced progenitor cell pool in AA, when used in appropriate culture conditions. The in vitro effects of flt3L on AA cells differ in many aspects from those of the structurally related cytokine SCF, suggesting a benefit in use of a combination of these two early-acting growth factors. SN - 0301-472X UR - https://www.unboundmedicine.com/medline/citation/9216732/Effect_of_flt3_ligand_on_in_vitro_growth_and_expansion_of_colony_forming_bone_marrow_cells_from_patients_with_aplastic_anemia_ L2 - http://www.diseaseinfosearch.org/result/556 DB - PRIME DP - Unbound Medicine ER -