Spaeth Erika L, Kidd Shannon, Marini Frank C
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Methods Mol Biol. 2012;904:173-90. doi: 10.1007/978-1-61779-943-3_15.
The act of migration is similar for many cell types. The migratory mechanism of mesenchymal stem cells (MSC) is not completely elucidated, yet many of the initial studies have been based on current understanding of the leukocyte migration. A normal function of MSC is the ability of the cell to migrate to and repair wounded tissue. This wound healing property of MSC originates with migration towards inflammatory signals produced by the wounded environment [1]. A tumor and its microenvironment are capable of eliciting a similar inflammatory response from the MSC, thus resulting in migration of the MSC towards the tumor microenvironment. We have shown MSC migration both in vitro and in vivo. In this chapter, we elucidate several in vivo methods to study MSC migration and mobilization to the tumor microenvironment. The first model is an exogenous model of MSC migration that can be performed in both xenograft and syngenic systems with in vitro expanded MSC. The second model utilizes transgenic-fluorescent--colored mice to follow endogenous bone marrow components including MSC. The third technique enables us to analyze data from the transgenic model through multispectral imaging. Furthermore, the migratory phenotype of MSC can be exploited for use in tumor-targeted gene delivery therapy has been efficacious in animal model studies and is an anticipated therapeutic device in clinical trials.
许多细胞类型的迁移行为相似。间充质干细胞(MSC)的迁移机制尚未完全阐明,但许多初步研究是基于目前对白细胞迁移的理解。MSC的正常功能是细胞迁移到受伤组织并进行修复的能力。MSC的这种伤口愈合特性源于其向受伤环境产生的炎症信号迁移[1]。肿瘤及其微环境能够引发MSC产生类似的炎症反应,从而导致MSC向肿瘤微环境迁移。我们已经在体外和体内证明了MSC的迁移。在本章中,我们阐述了几种研究MSC向肿瘤微环境迁移和动员的体内方法。第一个模型是MSC迁移的外源性模型,可在异种移植和同基因系统中使用体外扩增的MSC进行。第二个模型利用转基因荧光标记小鼠追踪包括MSC在内的内源性骨髓成分。第三种技术使我们能够通过多光谱成像分析来自转基因模型的数据。此外,MSC的迁移表型可用于肿瘤靶向基因递送治疗,在动物模型研究中已证明有效,并且是临床试验中预期的治疗手段。