Research in Vascular Composite Allotransplantation (VCA) aims to improve immunosuppression protocols for VCA patients. Compared to solid organ transplantation (SOT), VCA recipients experience a higher rate of acute rejection episodes, primarily targeting the skin, within the first year. To develop tailored immunosuppression protocols, immune responses following VCA, skin, and heart transplantation in allogeneic mouse models were investigated.
Our experimental studies delineated the role of dendritic cells (DCs), DC1 and DC2 subsets, and overall antigen-presenting cells (APCs) in the immune response. Additionally, numbers of T cells, B cells, and NK cells were evaluated, along with an analysis on tissue gene expression and cytokine blood and tissue levels. Significant differences in the immune responses and graft outcomes were observed and identifed as organ-specific.
Vascular thrombosis was identified as the primary cause of graft loss in the mouse hind limb transplantation model. To address this, researchers developed an anticoagulation protocol combining standard anticoagulation protocols with Low-Molecular-Weight Heparin (LMWH), leading to improved success rates. Results are accepted for publication in Plastic and Reconstructive Surgery - Global Open.
Furthermore, a rat model of bicornuate uterus transplantation was established. This model provides the basis for ongoing work on the impact of senescent cells with a senescence-associated secretory phenotype (SASP) on organ quality and immunogenicity. Moreover, the role of menopause and strategies for the elimination of senescent cells are currently evaluated. Preliminary results support an accumulation of senescent cells in parallel to age and hormonal changes.
In collaboration with the Transplant Surgery Research Laboratory of Prof. Tullius in Boston we investigated age and sex-dependent effects on alloimmunity using experimental skin and heart transplant models. Graft survival was inferior in young female recipients, and ovariectomies in young female mice prolonged survival, suggesting a key role of estrogens in modulating alloimmune responses. Dr. Friederike Martin received a 2-year DFG funding to carry out research at the lab of Prof. Tullius exploring sex-dependent differences in alloimmunity. She is also investigating the effects of estrogen levels and estrogen receptor alpha (ERa) on immune cells.
We have also completed all preparatory steps for a clinical uterus transplantation program at the Charite in cooperation with Prof. Dr. Jalid Sehouli (Department of Gynecology, Charite) and the pioneer for this procedure, Prof. Dr. Mats Brannstram (Department of Obstetrics & Gynecology, Sahlgrenska Academy, University of Gothenburg).
Moreover, Prof. Tullius will continue to be engaged in the Charite's efforts to establish an organ assessment and reconditioning unit.