Quality Assurance
Ongoing

6R in Organ Model Research

6R: 3R (Replace, Reduce, Refine) + Robustness, Registration, Reporting in Organ Model Research

Advanced in vitro models have strong potential to complement or substitute animal experiments and improve translational research. We collaborate with organ model researchers to develop and implement measures towards robust organ models and enhance their broad acceptance via 6R strategies.

Background / Rationale

Human organ models (organoids, multiphysiological systems, chips, explants, etc.) open up unique opportunities for the study of human diseases and the targeted treatment design. There is growing evidence that 3D organ models can better reflect human biology than traditional 2D cell cultures and many animal models.

However, crucial for the broad acceptance and successful application of these alternative methods in translational biomedical research is the demonstration of their reliability and robustness. Our team at the QUEST Center is working on the following two 6R projects with organ model researchers in Germany:

6R cross-sectional project in the Einstein Center 3R Berlin
The QUEST Center is a partner in the Einstein Center 3R Berlin and leads the "6R cross-sectional project", with the goal to extend the 3R focus (Replace, Reduce, Refine) by additional 3Rs: Robustness, Registration, Reporting.
You can find further information about EC3R here.
Objectives
Our goal is to increase the robustness of 3D organ models in EC3R projects, to achieve reproducible results, and to enable the transferability and dissemination of these alternative model systems in close collaboration with EC3R experts.
Methodology
Together with researchers at EC3R, we investigate the validity of the developed organ models in the research projects.
We support the research groups by advocating for a detailed documentation of the experimental procedures, thus increasing transparency in the research field and the reproducibility of the model systems. Here, the external validity and adaptability of organ models should be demonstrated by their implementation in partner laboratories. Additionally, we accompany various transfer processes and dissemination strategies of human organ models from the EC3R laboratories into the Berlin research landscape and beyond.
Expected results / Implications / Perspectives
The development and application of the 6R principles in organ model research will increase transparency in this innovative research field, and will provide measures towards robust and reproducible models and results. We will make our findings available to the research community to further advance the broad acceptance of organ model systems as innovative disease models and alternatives to selected animal models.

Systematic Reviews for in vitro organ models
Systematic reviews are a recognized method in clinical research to generate evidence-based knowledge and inform future research. This comprehensive and objective summary of published studies and their assessment has not been established for exploratory in vitro research yet. At the QUEST Center we are working with the CAMARADES Berlin team on several pilot projects to adapt the methodology of a systematic review to biomedical in vitro research.
Objectives
Our team is leading several systematic reviews to evaluate the current state of research and the application of alternative models in biomedical research. These evidence-based compilations can inform further research questions and enable researchers to define quality and documentation standards.
Methodology
We are conducting various systematic reviews assessing the literature around alternative model systems.
Currently, we are conducting a large-scale systematic review representing the impact of human organ models on COVID-19 research together with a team of 35 organ model researchers from EC3R and from all over Germany. In this review, experimental, quantitative and qualitative information will be extracted and analysed from the published literature (you can find the pre-registration of this systematic review here).
In another systematic review, we are focusing on the technical advances and reporting quality around bioprinted liver models (for pre-registration of this systematic review, please see here).
Expected results / Implications / Perspectives
In collaboration with the CAMARADES Berlin team, we are establishing new methodological strategies for conducting systematic reviews in biomedical in vitro research. Especially for the fast-moving research field around organ model development, systematic reviews are a promising measure to comprehensively demonstrate the impact and potential of alternative models.
The ongoing systematic review on the role of human organ models in COVID-19 research will highlight which models, assays and results were delivered, and how the quality of the published data can be assessed.

HOPE-IBD: Transdisciplinary Exchange for Relevant Preclinical Models
As part of the 6R project, the "HOPE-IBD" project was developed in collaboration with the Responsible PrecliniX unit, researchers at the BIH QUEST Centre for Responsible Research, and researchers from the EC3R. HOPE-IBD is a transdisciplinary research project that brings together perspectives from science, medicine, and lived experience to make preclinical and clinical research on Inflammatory Bowel Diseases (IBD) more patient-relevant and translationally meaningful.

Objectives
The aim of HOPE-IBD is to improve the translational relevance of preclinical research on inflammatory bowel diseases (IBD) by strengthening the link between preclinical findings, clinical practice, and patient-relevant outcomes.
Methodology
The project builds on a systematic literature review to identify outcome measures and parameters used in preclinical (animal and cell-based) and clinical IBD studies. Based on this evidence, patients, clinicians, preclinical researchers, and experts from industry and regulatory bodies are brought together in focus groups and a subsequent consensus workshop. These formats are used to discuss which outcomes are most relevant in clinical care and everyday life with IBD, and how they can be meaningfully represented in animal and cell culture models. Findings are integrated through a structured consensus process.
Expected Results / Implications / Perspectives
The main outcome will be a practical guidance document for preclinical IBD research, published Open Access. In addition, the results will be translated into accessible formats and disseminated via patient organizations. By aligning preclinical outcome selection with clinical relevance and patient priorities, HOPE-IBD aims to support more comparable, patient-centered, and translationally meaningful preclinical studies.
In addition to the Einstein Foundation, the project is funded in the area of patient engagement by a grant from the BUA TD-Lab. Further information is available here.