Cytokine-induced selective expansion and maturation of erythroid versus myeloid progenitors from purified cord blood precursor cells.
Cytokine-induced selective expansion and maturation of erythroid versus myeloid progenitors from purified cord blood precursor cells.
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DOI：
10.1182/blood.v81.12.3252.bloodjournal81123252
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发表时间：
1993
期刊：
影响因子：
20.3
通讯作者：
H. Mayani;W. Dragowska;P. Lansdorp
中科院分区：
文献类型：
--
作者：
H. Mayani;W. Dragowska;P. Lansdorp
为了研究不同细胞因子组合对高度纯化的原始祖细胞的增殖和分化的作用，使用无血清液体培养系统结合培养中产生的细胞的表型和功能分析。本研究选择通过流式细胞术和细胞分选从脐带血中纯化的CD 34 + CD 45 RAlo CD 71 lo细胞，因为它们具有高含量的克隆原细胞（34%），特别是多能祖细胞（CFU-MIX，所有细胞的12%）。检测了四种细胞因子组合：（1）肥大细胞生长因子（2）MGF、IL-6、IL-3和促红细胞生成素（Epo）;（3）MGF、IL-6、粒细胞-巨噬细胞集落刺激因子（GM-CSF）/IL-3融合蛋白（FP）、巨噬细胞集落刺激因子（M-CSF）和粒细胞-CSF（G-CSF）;（4）MGF、IL-6、FP、M-CSF、G-CSF和Epo。在存在MGF、IL-6、IL-3和Epo的情况下观察到红系祖细胞（BFU-E，高达55倍增加）和成熟红系细胞的最大数量，而在补充有MGF、IL-6、FP、M-CSF和G-CSF的培养物中发现髓系祖细胞（CFU-C，高达70倍增加）和成熟髓系细胞的最大水平。当存在MGF、IL-6、FP、M-CSF、G-CSF和Epo时，观察到红系和髓系祖细胞及其后代的最大水平。这些结果表明，特定的细胞因子组合可以直接作用于原始造血细胞，导致祖细胞数量的显着扩增，并影响其总体模式的增殖和分化。此外，本研究中提出的观察结果表明，所使用的细胞因子组合不能偏向多能祖细胞的谱系定型，而是对谱系限制性克隆形成细胞的发育具有允许作用。
To study the role of different cytokine combinations on the proliferation and differentiation of highly purified primitive progenitor cells, a serum-free liquid culture system was used in combination with phenotypic and functional analysis of the cells produced in culture. CD34+ CD45RAlo CD71lo cells, purified from umbilical cord blood by flow cytometry and cell sorting, were selected for this study because of their high content of clonogenic cells (34%), particularly multipotent progenitors (CFU-MIX, 12% of all cells). Four cytokine combinations were tested: (1) mast cell growth factor (MGF; a c-kit ligand) and interleukin-6 (IL-6); (2) MGF, IL-6, IL-3, and erythropoietin (Epo); (3) MGF, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF)/IL-3 fusion protein (FP), macrophage colony-stimulating factor (M-CSF), and granulocyte-CSF (G-CSF); and (4) MGF, IL-6, FP, M-CSF, G-CSF, and Epo. Maximum numbers of erythroid progenitors (BFU-E, up to 55-fold increase) and mature erythroid cells were observed in the presence of MGF, IL-6, IL-3, and Epo, whereas maximum levels of myeloid progenitors (CFU-C, up to 70-fold increase) and mature myeloid cells were found in cultures supplemented with MGF, IL-6, FP, M-CSF, and G-CSF. When MGF, IL-6, FP, M-CSF, G-CSF, and Epo were present, maximum levels of both erythroid and myeloid progenitors and their progeny were observed. These results indicate that specific cytokine combinations can act directly on primitive hematopoietic cells resulting in significant expansion of progenitor cell numbers and influencing their overall patterns of proliferation and differentiation. Furthermore, the observations presented in this study suggest that the cytokine combinations used were unable to bias lineage commitment of multipotent progenitors, but rather had a permissive effect on the development of lineage-restricted clonogenic cells.