Tissue resident mesenchymal cells: friend or foe in chronic graft-versus-host disease after hematopoietic stem cell transplantation

• Applicants: Professor Dr. Olaf Penack; Dr. Pedro Vallecillo García
• Subject Area: Hematology, Oncology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 544722947

Chronic graft-versus-host disease (cGVHD) frequently causes mortality and morbidity after allogeneic hematopoietic stem cell transplantation (alloSCT). There is a high medical need for new therapies as current standard immunosuppressive treatments rarely lead to complete responses and often cause severe side effects. Tissue resident mesenchymal cells mediate beneficial biologic processes, such as modulation of inflammation and containment of vascular integrity during inflammatory diseases. On the other hand, tissue resident mesenchymal cells are important contributors to pathologic fibrosis during chronic inflammation. Which factors lead to pathologic mesenchymal cell responses have not been identified in detail, impeding the development of therapeutic approaches. During cGVHD, we do not know the exact cellular and molecular mechanisms how GVHD-related fibrosis develops, progresses or resolves. Our preliminary data shows that a transition from endothelial cells to mesenchymal cells occurs during cGVHD. These data are a starting point to better understand the development of the typical cGVHD phenotype, characterized by tissue fibrosis and vascular rarefaction. The objective of this project is to better define the relationship between inflammation, fibrosis, damage and healing during cGVHD with a focus on tissue resident mesenchymal cells and their interactions with endothelial cells and macrophages. We will work with characterized animal models of cGVHD as well as with patient material. Our specific aims are: The results from the planned experiments could contribute to: 1) A better understanding of the underlying mechanisms of mesenchymal and endothelial cell dysfunction during cGVHD. 2)The translational development of therapeutic strategies aiming to adjust mesenchymal cell malfunction in order to decrease pathologic fibrosis.

• DFG Programme: Research Grants
• International Connection: France, Greece
• Cooperation Partners: Professorin Dr. Vasiliki Koliaraki; Dr. Mickael Orgeur