Perianale Fisteln bei CED: vom Mausmodell zur Klinik

Abstract

Fisteln stellen nach wie vor eine der wichtigsten Komplikationen bei Patienten mit Morbus Crohn dar. Bei mindestens einem Drittel aller Morbus Crohn Patienten treten im Laufe der Erkrankung Fisteln auf. Eine dauerhafte Heilung der Fistel wird jedoch, auch unter Ausschöpfung sämtlicher medikamentöser und chirurgischer Therapieoptionen, nur in rund einem Drittel dieser Patienten erreicht. Der genaue molekulare Mechanismus der Fistelentstehung ist bis heute nicht ganz klar. Aus histopathologischer Sichtweise stellen Fisteln eine röhrenartige Struktur dar, welche von flachen epithelartigen Zellen ausgekleidet ist. Als ursächlicher Entstehungsmechanismus wird dabei die sogenannte epitheliale-zu-mesenchymale Transition (EMT) angesehen und es kann eine starke Expression der Entzündungsmediatoren Tumor Nekrose Faktor, Interleukin-13 und Transforming Growth Factor β in den Fistelarealen nachgewiesen werden. Zusätzlich zu den bereits etablierten, medikamentösen Therapieoptionen, also Antibiotika, Immunmodulatoren und anti-TNF Antikörper, stellt insbesondere der Einsatz der mesenchymalen Stammzelltherapie einen erfolgversprechenden Therapieansatz für die Zukunft = Perianal fistulas in CED: from mouse model to clinic Abstract. Fistulas are one of the most severe complications in Crohn's disease patients (CD). More than one third of Crohn's disease patients will suffer from mainly perianal fistulas during the course of their disease. Options for fistula treatment are scarce and their efficacy is often insufficient. In particular, complex fistulas often can only insufficiently be treated and complete and longstanding fistula closure occurs only in about one third of the patients. One of the big challenges in this area is that, on the one hand, fistula pathogenesis is only partially understood, and, on the other, no well-established in vivo model for Crohn's fistula exists that could be used for preclinical studies. From a histopathologic perspective, a fistula is a tube-like formation that is covered by epithelial-like cells. Our current research findings suggests that fistulas development in Crohn's disease patients due to epithelial-to-mesenchymal transition (EMT) which occurs during wound healing and invasive cell growth. Cytokines and growth factors, such as TNF, IL-13 and TGFβ, seem to play a prominent role during fistula development. Current treatment strategies for Crohn's fistula include medcial treatment as well as surgical approaches, often used in combination. Routinely used medications mainly include antibiotics, immunosuppressives and anti-TNF antibodies. Recent studies also indicate that adipose tissue-derived or bone marrow-derived mesenchymal stem cells might be a promising novel approach for fistula therapy. However, often available medications are insufficient and surgery is needed what often also does not provide durable relief. So, it is obvious that novel treatment approaches are urgently needed to improve our understanding of fistula pathogenesis and to develop novel therapeutic strategies for the patients.