Immunomodulatory abilities of periodontal MSC subpopulations

Content of the research project. Mesenchymal stem/stromal cells (MSCs) are present in almost all adult tissues, including dental tissues, and are able to transform into different functional cells. It is thought that MSCs serve as cell reservoirs used for physiological tissue renewal and tissue repair after damages. In the last years, it appeared that MSCs could also modulate the activity of different immune cells, which is called immunomodulatory properties. Usually, MSCs exert anti-inflammatory effects and suppress the activity of the immune system. Interestingly, the immunomodulatory activity of MSCs is enhanced by activated immune cells. Thus, we can talk about the reciprocal interaction between MSCs and immune cells. Recent studies suggest that dental MSCs are not a homogenous population and comprise several subpopulations. These subpopulations can be distinguished based on the presence of specific markers on their surfaces. It is already known that different MSCs subpopulations have distinct abilities to transform into various adult cells, but the immunomodulatory abilities of different subpopulations have been never studied before. Hypothesis. The main hypothesis of this project is that different subpopulations of periodontal MSCs possess different immunomodulatory activities. We further hypothesize that these subpopulations might play different roles in the disease of the tooth-supporting tissue and regeneration of various dental tissues. Thus, this project is designed to understand the role of various dental MSCs subpopulations. Methods. We will use dental tissues from extracted human teeth and will isolate MSCs from them. Afterward, we will separate these MSCs into different subpopulations. These MSCs subpopulations will be co- cultured with various immune cells using an especially developed model, which is thought to reproduce in vivo situations. We will measure the properties of both MSCs and immune cells to understand how they interact. Finally, we will also use the teeth extracted from diseased patients, which will allow us to understand the role of different MSCs subpopulations in the disease of tooth- supporting tissues. Explanation indicating what is new/special about the project. The data obtained in this project will unravel how different subpopulations of dental MSCs interact with the immune system. The results of this project will allow us to understand the potential role of different MSCs subpopulations in the pathogenesis of the diseases of tooth-supporting tissues and pinpoint novel therapeutic approaches for dental regeneration. To summarize, this project will contribute to figure out those MSC subpopulations with best requirements for highly specialized tasks for their clinical application in oral and extra-oral tissues.