Bioartificial vascularized lymph node equivalents in the arteriovenous loop model

• Applicant: Privatdozentin Dr. Anja Miriam Boos
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 565203467

Damage to the lymphatic vessel and nodal system can lead to the development of lymphedema and is often the result of various therapeutic treatments for cancer. In recent years, surgical treatment options for lymphedema have been developed with the transplantation of vascularized lymph node packages VLNT. If cultured lymph nodes were used, morbidities associated with the VLN would be eliminated. In addition, the treatment technique would no longer be limited by the amount of transplantable tissue present in the patient. Our goal is to use the arteriovenous loop model to generate tissue that is able to drain lymph. This should be done using two complementary approaches to recreate the physiological processes. The processes occurring in lymph node development will be recreated using adult cell populations - first in vitro and then in vivo in the arteriovenous (AV) loop model. Lymph node systems arise physiologically through the interaction of lymphoid LTi cells and mesenchymal LTo cells. LTi stimulate LTo to express cytokines and adhesion proteins via lymphotoxin α1β2 (LT α1β2). These in turn recruit additional lymphocytes into the lymph node system. Mesenchymal stem cells (MSCs) are similar to LTo in various respects (morphology, cellular markers) and could potentially replace LTo in tissue engineering (TE). LTi are assigned to the Innate Lymphoid Cells (ILC), a lymphoid cell population that is also present in adult tissues. In addition, a network of lymphatic vessels will be created in the AV loop tissue by implanting spheroids made of lymphatic endothelial cells. These vessels can sprout upon autologous transplantation and improve lymphatic vascularization at the defect site. With human ADSC (adipose derived stem cells) we have already shown the basic feasibility of using them as an “LTo-like” cell population in vitro. In order to be able to characterize the interaction with cells of the immune defense more precisely in the rat model organism and to carry out studies on the drainage function, it is necessary to transfer the knowledge gained to rat cells. Here too, the feasibility has already been demonstrated in initial experiments in the rat model. After further characterization in the bioreactor, the cells are planned to be implanted into the rat's arteriovenous loop system (AV loop) in order to be able to grow bioartificial vascularized lymph node equivalents. In addition to the analysis of the colonization of the lymph node equivalents and their immunological integration, indocyanine green (ICG) lymphography and intravital contrast-enhanced ultrasound and MRI imaging will be used to show whether the tissue generated by both approaches is functional with regard to lymphatic drainage. This study thus paves the way for preclinical large animal experiments.

• DFG Programme: Research Grants