巨噬细胞迁移抑制因子对干细胞的作用

Role of macrophage migration inhibitory factor for stem cells

背景:干细胞是一种可以自我更新并且具有分化潜能的细胞,干细胞治疗是一种很有前景的治疗方法。巨噬细胞迁移抑制因子几乎在所有哺乳动物细胞中都有表达,对许多生理过程至关重要。现有研究证明,巨噬细胞迁移抑制因子在多种干细胞上表达并且调节多种干细胞的增殖、分化和迁移。目的:描述巨噬细胞迁移抑制因子的基本特征并着重阐述巨噬细胞迁移抑制因子对于干细胞的作用及机制。方法:在PubMed和中国知网数据库中检索近10年文献,英文检索词为“macrophage migration inhibitory factor,cancer stem cell,embryonic stem cell,neural stem cell,mesenchymal stem cell,endothelial progenitor cell,stem cell therapy,tissue engineering”,中文检索词为“巨噬细胞移动抑制因子、肿瘤干细胞、胚胎干细胞、神经干细胞、间充质干细胞、内皮祖细胞、干细胞治疗、组织工程”,经过文题、摘要的筛选,排除相关性差及陈旧和重复的文献,对最终符合标准的85篇文献进行综述。结果与结论:(1)巨噬细胞迁移抑制因子蛋白由3个亚基构成,在细胞表面通过与受体CD74,CD44,CXCR2,CXCR4和CXCR7产生作用。巨噬细胞迁移抑制因子储存在细胞内,通过非经典途径分泌,多种因素能影响其表达以及分泌。(2)巨噬细胞迁移抑制因子通过不同的信号通路促进肿瘤干细胞的迁移、侵袭、转移、逃逸和致瘤性。(3)当前研究中,比较明确的是巨噬细胞迁移抑制因子促进小鼠胚胎干细胞的神经分化。(4)巨噬细胞迁移抑制因子通过多个信号通路促进神经干细胞的增殖和存活。(5)巨噬细胞迁移抑制因子作用于间充质干细胞能够抑制凋亡、促进存活、延缓衰老并增加间充质干细胞的旁分泌作用,除此之外,巨噬细胞迁移抑制因子也证明可以通过结合受体CD74抑制间充质干细胞的归巢。(6)多项研究证明巨噬细胞迁移抑制因子通过CXCR4受体激活下游信号通路促进内皮细胞的迁移以及血管重建。(7)巨噬细胞迁移抑制因子作用于肿瘤干细胞、胚胎干细胞、神经干细胞、间充质干细胞、内皮祖细胞,对它们的增殖、分化、迁移和凋亡等过程产生影响,但其中部分作用还存在争议,确切机制需要更进一步验证。

BACKGROUND: Stem cells are self-renewing cells with differentiation potential and stem cell therapy is a promising therapeutic approach. Macrophage migration inhibitory factor is expressed in almost all mammalian cells and is essential for many physiological processes. Current studies have demonstrated that macrophage migration inhibitory factor is expressed on a variety of stem cells and regulates the proliferation, differentiation and migration of many stem cells.OBJECTIVE: To describe the basic characteristics of macrophage migration inhibitory factor and to elaborate on the role and mechanism of macrophage migration inhibitory factor on stem cells.METHODS: PubMed and CNKI databases were searched for relevant articles published in the past ten years. The key words were “macrophage migration inhibitory factor, cancer stem cell, embryonic stem cell, neural stem cell, mesenchymal stem cell, endothelial progenitor cell, stem cell therapy, tissue engineering” in Chinese and English, respectively. After removal of poorly related, outdated, and duplicate studies by reading the title and abstract, 85 articles were finally included in result analysis.RESULTS AND CONCLUSION:(1) Macrophage migration inhibitory factor protein consists of three subunits that interact on the cell surface by interacting with receptors CD74, CD44, CXCR2, CXCR4 and CXCR7. Macrophage migration inhibitory factor is stored intracellularly and secreted through non-classical pathways,and a variety of factors can affect macrophage migration inhibitory factor expression as well as secretion.(2) Macrophage migration inhibitory factor promotes migration, invasion, metastasis, escape and tumorigenicity of tumor stem cells through different signaling pathways.(3) Currently, it is relatively clear that macrophage migration inhibitory factor promotes neural differentiation of mouse embryonic stem cells.(4) Macrophage migration inhibitory factor promotes the proliferation and survival of neural stem cells through multiple signaling pathways.(5) Macrophage migration inhibitory factor acts on mesenchymal stem cells to inhibit apoptosis, promote survival, delay senescence, and increase paracrine effects of mesenchymal stem cells. In addition, macrophage migration inhibitory factor has also been shown to inhibit mesenchymal stem cell homing by binding to the receptor CD74.(6) Several studies have demonstrated that macrophage migration inhibitory factor activates downstream signaling pathways through CXCR4 receptors to promote endothelial cell migration and revascularization.(7) Macrophage migration inhibitory factor acts on tumor stem cells, embryonic stem cells, neural stem cells, mesenchymal stem cells, and endothelial progenitor cells to affect their proliferation, differentiation, migration, and apoptosis processes. Some of these effects are still controversial, and the exact mechanisms need to be further verified.