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Effect of stem cell factor (c-kit ligand), granulocyte-macrophage colony stimulating factor and interleukin 3 on hematopoietic progenitors in human long-term bone marrow cultures.
Stem Cells. 1993 Sep; 11(5):435-44.SC

Abstract

In this paper we attempt to improve upon the methods of hematopoietic stem cell expansion. We evaluate the effects of recombinant human stem cell factor (SCF or c-kit ligand) alone and also in combination with recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 3 (IL-3), on cell proliferation and differentiation in human long term bone marrow cultures (LTBMC). Weekly addition of 5 ng/ml of SCF with 25% serum containing media resulted in increased recovery of total nonadherent cells, granulocyte-macrophage colony forming units (CFU-GM), and burst-forming units erythroid (BFU-E) at week 1, but the number of bone marrow (BM) progenitor cells fell below the level of untreated control cultures at weeks 3 (BFU-E) and 4 (CFU-GM). At week 8, when the cultures were terminated, the CFU-GM recovery was markedly reduced in flasks supplemented with SCF compared with the controls (p < 0.002). Moreover, SCF treatment induced the early disappearance of BFU-E. When LTBMC were supplemented with the combination of SCF plus GM-CSF (100 U/ml) and IL-3 (5 ng/ml), synergistic activity of the CSFs was observed at week 1. The number of BM colony forming cells (CFC) rapidly declined below the level of growth factor-free controls, leading to the early exhaustion of the culture when SCF was combined with GM-CSF. By comparison, GM-CSF and IL-3 alone induced a statistically significant increase above the controls (no growth factor) in the number of nonadherent cell colonies of CFU-GM and BFU-E. Analysis of adherent layer cells from cultures supplemented with SCF showed increased cellularity, no adipogenesis, and early disappearance of myeloid progenitors while the percentage of CFU-GM in S phase, assessed by cytosine arabinoside (Ara-C) suicide assay, was 9.2 +/- 5% SD versus 27.7 +/- 10% SD in control (no growth factor) samples (p < 0.01). SCF increased the number of fibroblast colony forming units (CFU-F) and also showed a synergistic activity (9.6-fold increase) when combined with IL-3. These findings suggest that SCF, GM-CSF and IL-3 exert their activity on different cell populations within the hematopoietic system. Further investigations are needed to optimize the use of SCF in supporting hematopoiesis.

Authors+Show Affiliations

Autologous Bone Marrow Transplant Team, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.No affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

7694721

Citation

Lemoli, R M., and S C. Gulati. "Effect of Stem Cell Factor (c-kit Ligand), Granulocyte-macrophage Colony Stimulating Factor and Interleukin 3 On Hematopoietic Progenitors in Human Long-term Bone Marrow Cultures." Stem Cells (Dayton, Ohio), vol. 11, no. 5, 1993, pp. 435-44.
Lemoli RM, Gulati SC. Effect of stem cell factor (c-kit ligand), granulocyte-macrophage colony stimulating factor and interleukin 3 on hematopoietic progenitors in human long-term bone marrow cultures. Stem Cells. 1993;11(5):435-44.
Lemoli, R. M., & Gulati, S. C. (1993). Effect of stem cell factor (c-kit ligand), granulocyte-macrophage colony stimulating factor and interleukin 3 on hematopoietic progenitors in human long-term bone marrow cultures. Stem Cells (Dayton, Ohio), 11(5), 435-44.
Lemoli RM, Gulati SC. Effect of Stem Cell Factor (c-kit Ligand), Granulocyte-macrophage Colony Stimulating Factor and Interleukin 3 On Hematopoietic Progenitors in Human Long-term Bone Marrow Cultures. Stem Cells. 1993;11(5):435-44. PubMed PMID: 7694721.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of stem cell factor (c-kit ligand), granulocyte-macrophage colony stimulating factor and interleukin 3 on hematopoietic progenitors in human long-term bone marrow cultures. AU - Lemoli,R M, AU - Gulati,S C, PY - 1993/9/1/pubmed PY - 1993/9/1/medline PY - 1993/9/1/entrez SP - 435 EP - 44 JF - Stem cells (Dayton, Ohio) JO - Stem Cells VL - 11 IS - 5 N2 - In this paper we attempt to improve upon the methods of hematopoietic stem cell expansion. We evaluate the effects of recombinant human stem cell factor (SCF or c-kit ligand) alone and also in combination with recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 3 (IL-3), on cell proliferation and differentiation in human long term bone marrow cultures (LTBMC). Weekly addition of 5 ng/ml of SCF with 25% serum containing media resulted in increased recovery of total nonadherent cells, granulocyte-macrophage colony forming units (CFU-GM), and burst-forming units erythroid (BFU-E) at week 1, but the number of bone marrow (BM) progenitor cells fell below the level of untreated control cultures at weeks 3 (BFU-E) and 4 (CFU-GM). At week 8, when the cultures were terminated, the CFU-GM recovery was markedly reduced in flasks supplemented with SCF compared with the controls (p < 0.002). Moreover, SCF treatment induced the early disappearance of BFU-E. When LTBMC were supplemented with the combination of SCF plus GM-CSF (100 U/ml) and IL-3 (5 ng/ml), synergistic activity of the CSFs was observed at week 1. The number of BM colony forming cells (CFC) rapidly declined below the level of growth factor-free controls, leading to the early exhaustion of the culture when SCF was combined with GM-CSF. By comparison, GM-CSF and IL-3 alone induced a statistically significant increase above the controls (no growth factor) in the number of nonadherent cell colonies of CFU-GM and BFU-E. Analysis of adherent layer cells from cultures supplemented with SCF showed increased cellularity, no adipogenesis, and early disappearance of myeloid progenitors while the percentage of CFU-GM in S phase, assessed by cytosine arabinoside (Ara-C) suicide assay, was 9.2 +/- 5% SD versus 27.7 +/- 10% SD in control (no growth factor) samples (p < 0.01). SCF increased the number of fibroblast colony forming units (CFU-F) and also showed a synergistic activity (9.6-fold increase) when combined with IL-3. These findings suggest that SCF, GM-CSF and IL-3 exert their activity on different cell populations within the hematopoietic system. Further investigations are needed to optimize the use of SCF in supporting hematopoiesis. SN - 1066-5099 UR - https://www.unboundmedicine.com/medline/citation/7694721/Effect_of_stem_cell_factor__c_kit_ligand__granulocyte_macrophage_colony_stimulating_factor_and_interleukin_3_on_hematopoietic_progenitors_in_human_long_term_bone_marrow_cultures_ L2 - https://doi.org/10.1002/stem.5530110511 DB - PRIME DP - Unbound Medicine ER -