2020 Call: Experimental toolkit to evaluate cell-based therapies in the mouse brain

Project OC-2020-002

For every 100 prospective therapies in clinical development, approximately 90 are never approved for clinical use. This unsatisfactory rate is especially high in the field of neurosciences, revealing the complex biology of the human brain and the necessity for improved preclinical validation of experimental treatments. Recent advances in stem cell biology and genetic engineering have caused cell therapies to become an emerging treatment paradigm for patients with permanent neurologic deficits (e.g. after a stroke). However, preclinical validation of cell therapies is not standardized and their outcomes can be highly variable and difficult to reproduce. Furthermore, validation studies require high numbers of and cause considerable distress to animals due to various experimental interventions.

Thus, we aim to develop an experimental toolkit to advance and standardize preclinical assessment of cell therapies after stroke in mice. We will allow continuous tracking of the transplanted cells within these animals using non-invasive bioluminescence imaging. The transplanted cells will be engineered to improve immune compatibility with the recipient mouse, thereby rendering the use of immunosuppressants obsolete. The mice’s recovery following cell transplantation will be assessed using a novel deep-learning software that will provide a more comprehensive understanding of complex behaviors after stroke. For in-depth characterization, transplanted single cells will be evaluated for functionality, morphology, and gene expression in the brain tissue. Using this experimental toolkit, we expect to reduce the total numbers of animals by ≈ 80% and substantially minimize the animals’ distress compared to that in comparable preclinical studies.

Dr Ruslan Rust
University of Zurich

Prof. Johannes Bohacek
ETH Zurich

Prof. Csaba Földy
University of Zurich

Dr Christian Tackenberg
University of Zurich
 

 

Contact