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（CD 90）在成纤维细胞、活化的内皮细胞、神经元和间充质干细胞（MSC）上表达。在以前的项目期间，我们证明了Thy-1是活化内皮细胞上的重要细胞粘附分子，介导白细胞和肿瘤细胞粘附和迁移到外周组织中。最近，我们发现Thy-1通过与β 3-整联蛋白的相互作用控制成纤维细胞、内皮细胞和肿瘤细胞中增殖和细胞死亡之间的平衡。Thy-1介导的细胞-细胞接触抑制导致细胞生长受限，并且通过这种方式，Thy-1似乎有助于维持组织稳态。此外，Thy-1控制成纤维细胞的分化。MSC在调节重要的生物过程如炎症、免疫反应、造血和组织再生中起着核心作用。由于MSC表达Thy-1以及β 3-整联蛋白，因此我们承担Thy-1对MSC的重要调节功能。在本项目中，我们将使用Thy-1缺陷小鼠和对照小鼠来研究Thy-1对MSC的增殖、分化和活化的调节作用。MSC上Thy-1表达对于控制生物过程如炎症过程、免疫反应、造血和组织再生的生理重要性将在相关小鼠模型中显示。此外，众所周知，MSC关键地参与调节不同免疫细胞以及造血干/祖细胞的增殖、分化和活化。由于这些靶细胞表达β 3-整合素，与MSC密切共定位和相互作用，我们将阐明Thy-1在MSC上表达对免疫应答和造血调节的作用和后果。就其免疫调节功能而言，MSC代表了有趣的和新的候选人，用于调节炎症过程，免疫反应，造血和组织再生。对Thy-1在MSC中作用的研究将有助于我们进一步了解MSC的免疫调节功能。基于这些知识，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.