Department of Tissue Regeneration, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
Tissue Eng Part B Rev. 2012 Apr;18(2):101-15. doi: 10.1089/ten.TEB.2011.0488. Epub 2011 Dec 22.
Among the various types of cell-to-cell signaling, paracrine signaling comprises those signals that are transmitted over short distances between different cell types. In the human body, secreted growth factors and cytokines instruct, among others, proliferation, differentiation, and migration. In the hematopoietic stem cell (HSC) niche, stromal cells provide instructive cues to stem cells via paracrine signaling and one of these cell types, known to secrete a broad panel of growth factors and cytokines, is mesenchymal stromal cells (MSCs). The factors secreted by MSCs have trophic, immunomodulatory, antiapoptotic, and proangiogenic properties, and their paracrine profile varies according to their initial activation by various stimuli. MSCs are currently studied as treatment for inflammatory diseases such as graft-versus-host disease and Crohn's disease, but also as treatment for myocardial infarct and solid organ transplantation. In addition, MSCs are investigated for their use in tissue engineering applications, in which their differentiation plays an important role, but as we have recently demonstrated, their trophic factors may also be involved. Furthermore, a functional improvement of MSCs might be obtained after preconditioning or tailoring the cells themselves. Also, the way the cells are clinically administered may be specialized for specific therapeutic scenarios. In this review we will first discuss the HSC niche, in which MSCs were recently identified and are thought to play an instructive and supportive role. We will then evaluate therapeutic applications that currently try to utilize the trophic and/or immunomodulatory properties of MSCs, and we will also discuss new options to enhance their therapeutic effects.
在各种细胞间信号传递方式中，旁分泌信号是指在不同类型的细胞之间通过短距离传递的信号。在人体中，分泌的生长因子和细胞因子除其他外，可指示增殖、分化和迁移。在造血干细胞 (HSC) 龛位中，基质细胞通过旁分泌信号向干细胞提供指导信号，其中一种已知分泌广泛的生长因子和细胞因子的细胞类型是间充质基质细胞 (MSCs)。MSCs 分泌的因子具有营养、免疫调节、抗凋亡和促血管生成特性，其旁分泌谱根据其对各种刺激的初始激活而变化。MSCs 目前被研究用于治疗炎症性疾病，如移植物抗宿主病和克罗恩病，也用于治疗心肌梗死和实体器官移植。此外，MSCs 还用于组织工程应用的研究，在该应用中，其分化起着重要作用，但正如我们最近所证明的那样，其营养因子也可能参与其中。此外，通过预处理或定制细胞本身，可以获得 MSCs 的功能改善。同样，细胞的临床给药方式也可能针对特定的治疗情况进行专门化。在这篇综述中，我们将首先讨论 HSC 龛位，最近在该龛位中鉴定出 MSCs，并且认为它们具有指导和支持作用。然后，我们将评估目前试图利用 MSCs 的营养和/或免疫调节特性的治疗应用，并讨论增强其治疗效果的新选择。
