Mechanisms of Immune Modulation by Mesenchymal Stromal Cells and Clinical Translation
Mechanisms of Immune Modulation by Mesenchymal Stromal Cells and Clinical Translation
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DOI：
10.2174/1566524011313050016
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发表时间：
2013-06-01
影响因子：
2.5
通讯作者：
Galipeau, J.
中科院分区：
文献类型：
--
作者：
Stagg, J.;Galipeau, J.
间充质基质细胞（MSCs）的细胞治疗是深入研究的焦点。一些临床试验，包括大规模安慰剂对照III期临床试验，目前正在评估自体和异体间充质干细胞治疗灾难性炎症性疾病的治疗潜力，包括类固醇难治性移植物抗宿主病（GvHD）、多发性硬化症（MS）和克罗恩病。作为抗癌生物疗法的载体，msc也正在被研究。我们在这里回顾了最近在我们对间充质干细胞免疫抑制特性的理解方面的进展。我们首先讨论离体培养条件对MSCs表型和功能的影响。其次，我们总结了MSCs抑制的免疫功能，重点是T细胞、B细胞、自然杀伤细胞和树突状细胞的功能。第三，我们讨论了新发现的与MSCs免疫抑制活性有关的途径，包括血红素加氧酶(HO)-1的表达、半凝集素的分泌、CCL2拮抗、T调节细胞（Treg）串扰和tnf - α刺激基因/蛋白6 （TSG-6）的产生。最后，我们回顾了控制MSC归巢的分子途径的文献，并讨论了最近使用MSCs治疗GvHD， MS和克罗恩病的临床数据。
Cell therapy with mesenchymal stromal cells (MSCs) is the focus of intensive investigation. Several clinical trials, including large-scale placebo-controlled phase III clinical trials, are currently underway evaluating the therapeutic potential of autologous and allogeneic MSCs for treatment of catastrophic inflammatory diseases, including steroid-refractory graft-versus-host disease (GvHD), multiple sclerosis (MS) and Crohn's disease. MSCs are also being investigated as carriers of anti-cancer biotherapeutics. We here review recent developments in our understanding of the immunosuppressive properties of MSCs. We firstly discuss the effects of ex vivo culture conditions on the phenotype and functions of MSCs. Secondly, we summarize the immune functions suppressed by MSCs with a focus on T cell, B cell, natural killer cell and dendritic cell functions. Thirdly, we discuss newly identified pathways responsible for the immunosuppressive activity of MSCs, including the expression of heme-oxygenase (HO)-1, the secretion of galectins, CCL2 antagonism, T regulatory cell (Treg) cross-talk and production of TNF-alpha stimulated gene/protein-6 (TSG-6). Finally, we review the literature on the molecular pathways governing MSC homing and discuss recent clinical data on the use of MSCs for treatment of GvHD, MS and Crohn's disease.