ProfessorGuenther Eissner

Endothelial and mesenchymal stem cells in Transplant Medicine The vascular endothelium is the primary target of transplant-related complications and responsible for the loss of organ function. This central role of endothelial damage makes it an ideal target for early diagnosis and later on for therapeutic intervention. This is the aim of this research, including (i) an in vitro monitoring of endothelial-specific immune reactions on an individual patient basis using patient-specific endothelial-like cells; and (ii) paving the way to a risk-adapted individualized cellular therapy with immunomodulatory mesenchymal stem cells and with specific drugs for the protection of the endothelium by the help of 3D in vitro disease models. Research also includes mechanistic and signal transduction studies leading to a better understanding of disease mechanisms and how to best apply personalized medicine. Tumor angiogenesis Defibrotide, an endothelial protective drug based on a polydisperse mixture of single-stranded deoxyribonuleotides, has turned out to inhibit tumor angiogenesis in in vitro and in vivo models. Most likely it works through the inhibition of endothelial cell migration that is a prerequisite for blood vessel formation and sprouting. One major goal of this research project is to unravel the signal transduction mechanisms of Defibrotide and its yet to be identified receptor(s) in order to optimize anti-tumor angiogenic strategies. Another important aspect will be to identify differences between normal and tumor-associated endothelial cells to assess their individual susceptibility to certain anti-cancer drugs. Inflammatory signal transduction Pro-inflammatory mediators, such as members of the tumor necrosis factor superfamily, contribute to the pleiotropy of immunologic cell-cell interactions by e.g. by reverse signaling of the membrane-bound forms of these cytokines. Understanding the signal transduction mechanisms underlying these complex effector functions will be key to the design of anti-inflammatory therapies. Recently, a participation in a European-wide consortium has been added, where we investigate the role of a fibrin-derived peptide (FX06) for the protection of human pulmonary endothelial cells after a COVID-19-triggered cytokine storm.