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 Journal Article
| Authors: | Lemoli, R. M.; Gulati, S. C. |
| Article Title: | 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 |
| 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), synergis‐tic 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 syner‐gistic 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. Copyright © 1993 AlphaMed Press |
| Keywords: | controlled study; human cell; cytarabine; cell proliferation; bone marrow cells; cells, cultured; cell cycle s phase; stem cell factor; bone marrow; granulocyte macrophage colony stimulating factor; cell differentiation; recombinant proteins; hematopoietic stem cells; fibroblasts; hematopoiesis; hematopoietic stem cell; cell adhesion; colony forming unit gm; colony forming cell; promyelocyte; adipocyte; granulocyte-macrophage colony-stimulating factor; interleukin 3; interleukin-3; burst forming unit e; human; article; support, non-u.s. gov't; hematopoietic cell growth factors; bone marrow culture; gm‐csf; il‐3; c‐kit ligand; colony forming unit f |
| Journal Title: | Stem Cells |
| Volume: | 11 |
| Issue: | 5 |
| ISSN: | 1066-5099 |
| Publisher: | AlphaMed Press |
| Date Published: | 1993-09-01 |
| Start Page: | 435 |
| End Page: | 444 |
| Language: | English |
| DOI: | 10.1002/stem.5530110511 |
| PUBMED: | 7694721 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2019 -- Source: Scopus |
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