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

• Applicant: Privatdozentin Dr. Anja Saalbach
• Subject Area: Dermatology
• Term: from 2008 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 53182997

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.

• DFG Programme: Research Grants
• Co-Investigator: Privatdozent Dr. Ulf Anderegg