Assessment of immunotoxicity using precision-cut tissue slices

Abstract

1. When the immune system encounters incoming infectious agents, this generally leads to immunity. The evoked immune response is usually robust, but can be severely perturbed by potentially harmful environmental agents such as chemicals, pharmaceuticals and allergens.2. Immunosuppression, hypersensitivity and autoimmunity may occur due to changed immune activity. Evaluation of the immunotoxic potency of agents as part of risk assessment is currently established in vivo with animal models and in vitro with cell lines or primary cells.3. Although in vivo testing is usually the most relevant situation for many agents, more and more in vitro models are being developed for assessment of immunotoxicity. In this context, hypersensitivity and immunosuppression are considered to be a primary focus for developing in vitro methods. Three-dimensional organotypic tissue models are also part of current research in immunotoxicology.4. In recent years, there has been a revival of interest in organotypic tissue models. In the context of immunotoxicity testing, precision-cut lung slices in particular have been intensively studied. Therefore, this review is very much focused on pulmonary immunotoxicology. Respiratory hypersensitivity and inflammation are further highlighted aspects of this review. Immunotoxicity assessment currently is of limited use in other tissue models, which are therefore described only briefly within this review.

Preclinical validation and imaging of Wnt-induced repair in human 3D lung tissue cultures

“…While previous reports have used precision-cut lung slices from rodent models and human tissue predominantly for short-term toxicological and pharmacological analysis [32][33][34][35][36], we report the application of 3D-LTCs of patient-derived lungs to study diseased lung tissue and potential lung repair in high spatiotemporal resolution. This represents a major advance in closing the preclinical gap in drug and therapy development, since it allows the evaluation of cell-matrix interaction as well as cellular function in human lung tissue.…”

Immunotoxicity, genotoxicity and epigenetic toxicity of nanomaterials: New strategies for toxicity testing?

“…Recently, several research groups published alternative approaches, using various cell lines -human Jurkat T-cell, human lymphoid T-cell (MOLT-4) or B-cell (IM-9), human acute myeloid leukemia HL-60 cell, murine Tcell (CTLL-2) or THP-1 (human monocytic cell line derived from acute monocytic leukemia patient) (Minervini et al, 2005;Schmeits et al, 2013Schmeits et al, , 2015Song et al, 2014;Markovi c et al, 2015). Precision-cut tissue slices are also being used (Sewald and Braun, 2013). …”

Preclinical safety and efficacy models for pulmonary drug delivery of antimicrobials with focus on in vitro models

“…However, the authors also mentioned that such experiments require a further improvement of the test protocol [25]. The potential of such models mimicking immune responses was reviewed by Sewald and Braun [26]. In future, the results of an ongoing pre-validation project including 20 substances investigated in three independent laboratories might give more insights in the applicability of lung slices [27].…”