Effect of Exogenously Applied Endothelial Cells in Thymic Regeneration After Hematopoietic Stem Cell Transplantation

• Applicant: Dr. Hana Andrlova
• Subject Area: Hematology, Oncology
• Term: from 2018 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 411447633

Recovery of the immune system after hematopoietic stem cell transplantation is a key process to avoid severe infectious complications and a cancer relapse. Thymic regeneration after an injury, such as chemotherapy, irradiation or graft versus host disease is necessary for regaining the immune competence. The host laboratory recently demonstrated that thymic endothelial cells can be isolated, expanded ex vivo (exECthy) and, when administered intravenously into mice receiving a sub-lethal total body irradiation, enhance thymic recovery. The major goal of the proposed project is to study the adoptive transfer of exECthy as a novel therapeutic approach to improve thymic and immune regeneration in recipients of hematopoietic cell transplantation (HCT). The exECThy isolated from the donor, recipient or a third mouse strain will be injected into mice that have received a syngeneic or allogeneic stem cell transplantation. The effect of this transfer on thymic regeneration, as well as peripheral T-cell reconstitution, T-cell function and T-cell receptor diversity will be evaluated. At the same time, the integration of exECThy in the thymus vasculature and ways to enhance this process will be studied. Adoptive administration of exECThy represents a novel cellular therapy promoting thymic function renewal in patients. Therefore, the results of the proposed project will serve as a starting point for the development of a clinically relevant immune-regenerative strategy.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Marcel van den Brink, Ph.D.