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027 | Human cerebroids derived from induced pluripotent stem cells in neuronal toxicity studies of glyphosate

Cellular and Molecular Neurobiology

Author: Gonzalo Germán Guendulain | email: gonzaloguendulain@mi.unc.edu.ar


Gonzalo Germán Guendulain , Florencia Linares , Monica Remedi , Laura  Gastaldi , Alfredo Cáceres , Ana Lis Moyano , Andrés Cardozo Gizzi

1° Centro de Investigación en Medicina Traslacional “Severo Amuchástegui” (CIMETSA) – Instituto Universitario Ciencias Biomédicas Córdoba (IUCBC)

The use of stem cells in translational medicine is nowadays one of the great promises of biomedical sciences. One of its short-term possible applications is the development of organoids, three-dimensional tissues capable of reproducing the cellular architecture and some organ-specific functions. Due to this, these models promise to increase the number of toxicity assays performed, and therefore to provide useful toxicological information to improve existing consumption regulations. In this project, we used a human induced pluripotent stem cell (hiPSCs) line to generate brain organoids. We implemented novel cell culture techniques that included a 3D-printed mini-bioreactor to culture the organoids. By immunostaining and confocal microscopy we confirmed the presence of radially arranged cell structures in them. These consist of concentric layers of neural progenitors towards the lumen and neurons towards the periphery, similar to those observed during the in vivo development of embryonic brain tissues. To evaluate their use as a biological platform for toxicity assays, we exposed them to Glyphosate, the most used herbicide in Argentina. We were able to observe both morphological changes and a diminished peripheral neuronal layer in the structures. Thus, our results constitute one of the first records of glyphosate evaluation in a human model and suggest that the herbicide is potentially neurotoxic to our species.