Charité 3^R Lecture: Born to be wild - utilizing the common link among mammals to create better translational research models

Event for expert public only

25.11.2021, 12-1 pm

Talk: Dr. med. Stephan Rosshart, Medical Center - University of Freiburg; Chair: Prof. Dr. Christoph Harms, Charité - Universitätsmedizin Berlin Im Original geändert

Charité 3^R and Einstein Center 3R invite Dr. med. Stephan Rosshart to present the wildling mice model and its potential to improve translational research:

Born to be wild - utilizing the common link among mammals to create better translational research models

The discussion will be moderated by Charité Prof. Dr. Christoph Harms and we are looking forward to your active participation.

Registration

Detailed Abstract by Dr. med. Stephan Rosshart:

Mouse models are paramount for research. However, they suffer from major shortcomings like irreproducible results rooted in divergent microbiota among institutions and the fact that the transition from studies in mice to bedside practice in humans rarely works. A vast body of literature shows that lab mice have not only misdirected clinical approaches consuming trillions of euros [1], but also caused fatal outcomes in human trials [2, 3]. The imperative question is: How can we solve these problems!?

Microbiome research may help to answer this question. Till recently, the limited translational value of the lab mouse was primarily attributed to differences in genetics between mice and humans. However, paradigm-shifting work has shown that lab mice are too far removed from natural conditions to faithfully mirror the physiology of free-living mammals like humans. Mammals and their immune systems evolved to survive and thrive in a microbial world and behave differently in a sanitized environment. This distorts how the immune system of ultra-clean lab mice develops and functions, leading to false assumptions of how the human immune system works.

To improve mouse models, three concepts were proposed. The “rewilding approach” houses lab mice in diverse seminatural-environments, the “dirty mouse approach” exposes lab mice to pathogens that may or may not represent natural exposure, and the “natural microbiota approach” implants embryos of lab mice into wild mice to create “wildlings”. Wildlings more closely resemble the natural mammalian metaorganism of humans with co-evolved microbes and pathogens while preserving the genetics of lab mice [4, 5]. 

Indeed, in preclinical trials, where rodent and non-human primate models failed to predict the human response to harmful drug treatments [2, 3], wildlings accurately phenocopied humans and could have prevented these catastrophically failed human trials [5]. Further, the microbiome of wildlings was stable over multiple generations and highly resilient against environmental challenges thereby providing an excellent model for long-term work and reproducible experimentation [4, 5].

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