Scharl Michael
1 Klinik für Gastroenterologie und Hepatologie, UniversitätsSpital Zurich.
Ther Umsch. 2019 Jan;75(5):287-294. doi: 10.1024/0040-5930/a001000.
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.
从小鼠模型到临床 摘要。瘘管是克罗恩病(CD)患者最严重的并发症之一。超过三分之一的克罗恩病患者在病程中主要会出现肛周瘘管。瘘管治疗选择匮乏,且疗效往往不佳。特别是,复杂瘘管常常难以得到充分治疗,只有约三分之一的患者能实现瘘管完全且长期闭合。该领域的一大挑战在于,一方面,瘘管发病机制仅得到部分理解,另一方面,尚无成熟的克罗恩病瘘管体内模型可用于临床前研究。从组织病理学角度来看,瘘管是一种由类上皮细胞覆盖的管状结构。我们目前的研究结果表明,克罗恩病患者的瘘管形成是由于伤口愈合和侵袭性细胞生长过程中发生的上皮-间质转化(EMT)。细胞因子和生长因子,如肿瘤坏死因子(TNF)、白细胞介素-13(IL-13)和转化生长因子β(TGFβ),似乎在瘘管形成过程中起重要作用。目前克罗恩病瘘管的治疗策略包括药物治疗以及手术方法,通常联合使用。常用药物主要包括抗生素、免疫抑制剂和抗TNF抗体。近期研究还表明脂肪组织来源或骨髓来源的间充质干细胞可能是一种有前景的瘘管治疗新方法。然而,现有药物往往效果不佳,且通常需要手术治疗,但手术也常常无法提供持久缓解。因此,显然迫切需要新的治疗方法来增进我们对瘘管发病机制的理解,并为患者开发新的治疗策略。