Human marrow-derived mesenchymal stem cells (MSCs) express hematopoietic cytokines and support long-term hematopoiesis when differentiated toward stromal and osteogenic lineages
Human marrow-derived mesenchymal stem cells (MSCs) express hematopoietic cytokines and support long-term hematopoiesis when differentiated toward stromal and osteogenic lineages
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DOI：
10.1089/152581600750062264
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发表时间：
2000-12-01
期刊：
影响因子：
--
通讯作者：
Gerson, SL
中科院分区：
文献类型：
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作者：
Majumdar, MK;Thiede, MA;Gerson, SL
人间充质干细胞（MSCs），骨髓来源的间充质多能贴壁细胞可以沿成骨、软骨、脂肪和肌腱生成谱系分化。在本报告中，我们描述了细胞因子和生长因子基因在MSCs中的表达，并研究了在成骨和间质分化过程中细胞因子表达的调节。MSCs组成性地表达白细胞介素(IL)-6、IL-11、白血病抑制因子（LIF）、巨噬细胞集落刺激因子（M-CSF）和干细胞因子（SCF）的mRNA。IL-1 α处理的MSCs上调了IL-6、IL-11和LIF的mRNA水平，并开始表达可检测水平的粒细胞集落刺激因子（G-CSF）、粒细胞巨噬细胞集落刺激因子（GM-CSF）。M-CSF和SCF的mRNA水平没有变化。在成骨培养基中培养的MSCs沿成骨谱系分化，IL-6、IL-11和LIF mRNA水平下调，而M-CSF和SCF表达不变，G-CSF和GM-CSF仍未检测到。在任何条件下MSC培养均未检测到IL-3。在对照培养基、IL-1 α或成骨培养基中预培养的MSCs保持类似的能力来支持长期培养起始细胞（LT-CIC）。因此，原代和成骨分化的间充质干细胞产生重要的造血细胞因子，并在长期培养中支持造血，这表明这些细胞可能在祖细胞扩增过程中为造血提供了良好的体外环境，并且可能对体内细胞治疗很重要。
Human mesenchymal stem cells (MSCs), bone marrow-derived pluripotent adherent cells of mesenchymal origin can differentiate along the osteogenic, chondrogenic, adipogenic, and tendonogenic lineages. In this report we characterize cytokine and growth factor gene expression by MSCs and investigate the modulation of cytokine expression that occurs during osteogenic and stromal differentiation. MSCs constitutively expressed mRNA for interleukin (IL)-6, IL-11, leukemia inhibitory factor (LIF), macrophage colony-stimulating factor (M-CSF), and stem cell factor (SCF). MSCs treated with IL-1 alpha upregulated mRNA levels of IL-6, IL-11, and LIF, and began to express detectable levels of granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF). mRNA levels of M-CSF and SCF did not change. MSCs cultured in osteogenic medium differentiated along the osteogenic lineage and downregulated mRNA levels of IL-6, IL-11 and LIF whereas, M-CSF and SCF expression were unchanged and G-CSF and GM-CSF remained undetectable. IL-3 was not detected in MSC culture under any conditions. MSCs precultured in control medium, IL-1 alpha, or osteogenic medium maintained similar capacity to support long-term culture initiating cell (LT-CIC). Thus, primary and osteogenic differentiated MSCs produce important hematopoietic cytokines and support hematopoiesis in long-term cultures, suggesting that these cells may provide an excellent ex vivo environment for hematopoiesis during progenitor cell expansion and mag be important for in vivo cell therapy.