Function of Thy-1 on mesenchymal stem cells: Impact for the regulation of biological processes like inflammation, immune responses, tissue regeneration, and hematopoiesis

Thy-1(CD90)表达于成纤维细胞、活化的内皮细胞、神经元和间充质干细胞(MSC)。在前期的研究中，我们已经证明Thy-1是一种重要的细胞黏附分子，可以在活化的内皮细胞上介导白细胞和肿瘤细胞向周围组织的黏附和迁移。最近，我们发现Thy-1通过与β3整合素的相互作用控制成纤维细胞、内皮细胞和肿瘤细胞的增殖和死亡之间的平衡。Thy-1介导的细胞-细胞接触抑制导致细胞生长受限，通过这种方式，Thy-1似乎有助于维持组织的动态平衡。此外，Thy-1控制成纤维细胞的分化。MSC在炎症、免疫反应、造血和组织再生等重要生物学过程中发挥核心调节作用。由于MSC表达Thy-1和β3整合素，因此Thy-1对MSC具有重要的调节作用。在本项目中，我们将利用Thy-1缺陷小鼠和对照组小鼠，研究Thy-1对MSC增殖、分化和激活的调控作用。在相关的小鼠模型中，MSC上Thy-1的表达对于控制炎症过程、免疫反应、造血和组织再生等生物学过程具有重要的生理意义。此外，众所周知，MSC在不同免疫细胞的增殖、分化和激活以及造血干/祖细胞的调控中起着关键作用。由于这些靶细胞表达β3整合素，与MSC紧密共定位并相互作用，我们将阐明MSC上Thy-1表达在免疫反应和造血调控中的作用和后果。就其免疫调节功能而言，MSC代表着有趣的新候选细胞，用于调节炎症过程、免疫反应、造血和组织再生。研究Thy-1在MSC中的作用有助于加深对MSC免疫调节功能的认识。基于这一知识，可以开发出在临床相关问题中使用MSC的新方法。

Thy-1 (CD90) is expressed on fibroblasts, activated endothelial cells, neurons and mesenchymal stem cells (MSC). During previous project periods we demonstrated that Thy-1 is an important cell adhesion molecule on activated endothelial cells mediating the adhesion and transmigration of leukocytes and tumor cells into peripheral tissues. Recently, we showed that Thy-1 controls the balance between proliferation and cell death in fibroblasts, endothelial cells and tumor cells via the interaction with beta3-integrins. Thy-1-mediated cell-cell-contact inhibition results in the limitation of cell growth and by this way Thy-1 seems to contribute to the maintenance of tissue homeostasis. Moreover, Thy-1 controls differentiation of fibroblasts.MSC are central in the regulation of important biological processes like inflammation, immune responses, hematopoiesis and tissue regeneration. Since MSC express Thy-1 as well as beta3-integrins we assume important regulatory functions of Thy-1 on MSC. In this project we will investigate the role of Thy-1 on MSC for the regulation of proliferation, differentiation and activation of MSC using Thy-1-deficient mice and control mice. The physiological importance of Thy-1 expression on MSC for the control of biological processes like inflammation processes, immune reactions, hematopoiesis and tissue regeneration will be shown in relevant mouse models. Furthermore, it is well-known that MSC are critically involved in the regulation of proliferation, differentiation and activation of different immune cells as well as of hematopoietic stem/progenitor cells. Since these target cells express beta3-integrins, closely co-localize and interact with MSC we will clarify the role and consequences of Thy-1 expression on MSC for the regulation of immune responses and hematopoiesis.In respect to their immune-modulating functions MSC represent interesting and new candidates for the modulation of inflammatory processes, immune reactions, hematopoiesis, and tissue regeneration. The investigations of role of Thy-1 on MSC will help to improve our understanding of the immune-modulating functions of MSC. Based on this knowledge new approaches for the use of MSC in clinical-relevant questions can be developed.