1. Human immunocompetent choroid-on-chip: A novel tool for studying ocular effects of biological drugs
- Author
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Schluender K, M. Mesquida, Lena Mesch, Christopher Probst, Stefan Liebau, Fischer Mj, Magdalene Weiss, Anneliese Schneider, Peter Loskill, Stefan Kustermann, Nicolini, Madalena Cipriano, Kevin Achberger, Linke K, Giusti Am, and Publica
- Subjects
Stromal cell ,QH301-705.5 ,CD3 ,medicine.medical_treatment ,Article ,chemistry.chemical_compound ,Immune system ,Antibodies, Bispecific ,Microchip Analytical Procedures ,medicine ,Humans ,Biology (General) ,Drug safety ,Eye diseases ,Inflammation ,Biological Products ,biology ,business.industry ,Choroid ,Endothelial Cells ,Retinal ,biochemical phenomena, metabolism, and nutrition ,medicine.anatomical_structure ,Cytokine ,chemistry ,Cancer research ,biology.protein ,Imaging the immune system ,Melanocytes ,bacteria ,sense organs ,Antibody ,Immunocompetence ,business - Abstract
Disorders of the eye leading to visual impairment are a major issue that affects millions of people. On the other side ocular toxicities were described for e.g. molecularly targeted therapies in oncology and may hamper their development. Current ocular model systems feature a number of limitations affecting human-relevance and availability. To find new options for pharmacological treatment and assess mechanisms of toxicity, hence, novel complex model systems that are human-relevant and readily available are urgently required. Here, we report the development of a human immunocompetent Choroid-on-Chip (CoC), a human cell-based in vitro model of the choroid layer of the eye integrating melanocytes and microvascular endothelial cells, covered by a layer of retinal pigmented epithelial cells. Immunocompetence is achieved by perfusion of peripheral immune cells. We demonstrate controlled immune cell recruitment into the stromal compartments through a vascular monolayer and in vivo-like cytokine release profiles. To investigate applicability for both efficacy testing of immunosuppressive compounds as well as safety profiling of immunoactivating antibodies, we exposed the CoCs to cyclosporine and tested CD3 bispecific antibodies., To address the key physiological characteristics related to choroidal drug reactions and its immunology, Cipriano et al. developed a human immunocompetent choroidal in vitro model that mimics the tissue vascularization, pigmentation and immune response in the presence of circulating immune cells. This could help building a toolbox of in vitro models recapitulating aspects of the immune system to study immuneoncology.
- Published
- 2022