Brain Organoids to Evaluate Cellular Therapies

Simple Summary Animal models are routinely used in pre-clinical studies to evaluate the safety and efficacy of novel therapies, such as cell transplantation, but have limited predictive value. In this study, we set up an experimental model using human stem cells grown in 3D, which form rudimentary brain structures in vitro, called brain organoids. We investigated the possibility of using these brain organoids to evaluate the safety of a cell therapy product, by comparing the results obtained in our model with the standard mouse model. Our results suggest that brain organoids can be informative in the evaluation of cell therapies, helping to reduce the number of animals used in regulatory studies. Animal models currently used to test the efficacy and safety of cell therapies, mainly murine models, have limitations as molecular, cellular, and physiological mechanisms are often inherently different between species, especially in the brain. Therefore, for clinical translation of cell-based medicinal products, the development of alternative models based on human neural cells may be crucial. We have developed an in vitro model of transplantation into human brain organoids to study the potential of neural stem cells as cell therapeutics and compared these data with standard xenograft studies in the brain of immunodeficient NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ (NSG) mice. Neural stem cells showed similar differentiation and proliferation potentials in both human brain organoids and mouse brains. Our results suggest that brain organoids can be informative in the evaluation of cell therapies, helping to reduce the number of animals used for regulatory studies.