Vascular Composite Tissue Allo-Transplantation

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Objective

The overall objective of our integrated basic and clinical research group Vascular Composite Tissue Allo-Transplantation is to study novel aspects of antigenicity, immune modulation and neo-vascularization in post-transplant rejection processes of VCA compared to solid organ and to skin transplantation. In the clinical section of the project, our goal is to establish a clinical bio-repository as a pre-requisite for a clinical research VCA program and to implement a clinical VCA research program (hand, abdominal wall and uterus) as a multi-disciplinary and translational effort.
The experiences made during the last years in clinical uterus transplantations suggests a necessity to include post-menopausal and brain dead donors to be able to fulfill the expected amount of uterus transplantations worldwide and demands a more detailed view on the immune regulation of the maternal-fetal interface to improve pregnancy and birth rates after UTx. A first successful transplantation of an uterus from a brain dead donor, including successful pregnancy and birth has been reported recently. With the upcoming need in mind, we want to analyze the influence of donor’s age on alloimmunity, fertility, pregnancy and fetal development in a preclinical rat uterus transplantation model. We will also compare the immunological state of the maternal-fetal interface from pregnant normal rats with pregnant rats following allogeneic uterus transplantation. The results of our proposed experiments could have a great impact on clinically relevant aspects in uterus transplantation, physiological pregnancies, VCA and overall transplantation medicine

Einstein BIH Visiting Fellow Prof. Tullius

Prof. Tullius is an Einstein BIH Visting Fellow funded by the Stiftung Charité and Einstein Foundation. He proved to be a perfect fit for the mission of the Charité as a leader in clinical medicine, research and education: Brigham and Women’s Hospital is home of the largest and most successful composite tissue transplantation program worldwide. The institution has performed seven face and three upper extremity transplants. Prof. Tullius has been responsible for the medical treatment, and the immunosuppressive protocol of all VCA patients. Moreover, the institution has been approved by UNOS as only one of three uterine transplant centers in the US.
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Current State of Research

VCA including hand, upper extremity, face, abdominal wall, uterus and urogenital transplantation has emerged from a visionary therapy option in the past to become an innovative reconstructive treatment modality for patients with tremendous tissue defects that are not amenable for conventional treatment protocols. Immunological, microsurgical as well as functional advancements, which are mostly based on basic science research, are responsible for this development and have introduced VCA to the clinical reality with encouraging results all over the world.

Uterus transplantation constitutes a new and to date the only therapeutic option to provide women with Absolute Uterine Factor Infertility (AUFI) the opportunity to carry biological babies. A spectrum of various pathologies ranging from congenital syndromes like Mayer-Rokitanski-Küster-Hauser-Syndrome (Müllerian malformation; estimated prevalence 1:4500 ) to the surgical removal of the uterus, e.g. in the event of severe postnatal bleeding, cervical cancer or the Asherman-Syndrome, all of which lead to preventing uterine implantation of an embryo or carrying out pregnancy to term.

The first delivery of a healthy baby after living donor UTx in 2014 marked a true milestone in the field of gynecology, reproductive medicine and transplant surgery all together. UTx has since become a rapidly expanding field with a total number of 13 newborns to date – including the first one following deceased donor transplantation in late 2017 . Its therapeutic potential and growing acceptance are reflected by an increasing number of clinical UTx-programs worldwide. In Germany, two UTx have been performed, however, no pregnancy has thus far been reported . There is strong demand for a UTx-program and the Charité in cooperation with Harvard Medical School is a perfect fit for this endeavor
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Dissemination of Information

We established a basic research program in the field of composite tissue transplantation and paved the way towards clinical programs in Berlin. We successfully formed a highly efficient interdisciplinary team addressing relevant basic research aspects in VCA – tolerance and chronic graft deterioration.

A full professorship for Plastic Surgery with the focus on vascularized composite tissue allotransplantation will be integrated into Prof. Tullius Berlin basic research group and the clinical team. This new position reflects the Charité’s interest in Prof. Tullius work in this field and the commitment of the host Prof. Pratschke and the Dept. of Surgery. Various internationally renowned experts applied for this position and will foster our efforts. The appointment committee shall draw up a shortlist of the three most suitable candidates in early spring 2019.
During Prof. Tullius’ first Berlin visit as an Einstein BIH Visiting Fellow in February 2017 an international symposium has been organized. The meeting ‘Transplantation in Transition’ focused on vascular composite tissue allotransplantation and served as a kick-off meeting for our interdisciplinary project. The meeting was held on February 25th, 2017 and was attended by international specialists in the field
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Our Team

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Prof. Dr. Stefan Tullius

Einstein BIH Visiting Fellow

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Head of Experimental Surgery

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Univ.-Prof. Dr. Johann Pratschke

Principal Investigator

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Executive Assistant

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Postdoc

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Priv.-Doz. Christian Witzel

Research Partner

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Prof. Dr. Jalid Sehouli

Research Partner

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Dr. Gülhan Inci

Research Partner

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Principal Investigator

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Research Assistant

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Peter Tang

Research Assistant

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