@article{6361,
  keywords = {Cell biology, Cellular neuroscience, Scientific community},
  author = {Laura Castro-Aldrete and Melanie Einsiedler and Carla Cuní-López and Quentin Vanhaelen and Antonia Silvestri and Maria Teresa Ferretti and Martina Elena de Gennaro and Guido Putignano and Maria Guix and Nicola Marino and Liisa A. M. Galea and Kerstin Lenk and Samantha Paoletti and Alex Zhavoronkov and Antonella Santuccione Chadha},
  title = {Modelling sex differences of neurological disorders in vitro},
  abstract = {Although in vitro models are valuable tools for modelling neurological disorders such as neurodegenerative diseases and neuropsychiatric disorders, it remains unclear whether and how biological sex characteristics should be considered when designing experiments. The historical failure to incorporate sex as a biological variable and acknowledge sex and gender differences in preclinical and clinical research has created a translation gap, which is only now beginning to be addressed. Sex effects are observed across mechanisms in common neuropsychiatric and neurodegenerative disorders. Therefore, it is imperative to incorporate sex differences into both in vitro and in vivo models to develop more precise and sustainable research tools for brain disorders. Such an approach will enable researchers to account for the physiological and pathological characteristics of male and female brains, improving the replicability and translatability of research results. In this Review, we discuss in vitro models of increasing complexity used for exploring pathological mechanisms and pharmacological target development. We address the advantages and challenges of using in vitro models to investigate sex differences in neurological disorders, starting with the types of cells used in in vitro models, including immortalized cell lines, primary cultures, induced pluripotent stem cells, up to 3D organoid and organ-on-a-chip models. Furthermore, we propose a roadmap and discussion of best practices to incorporate sex as a biological variable into in vitro models of neurodegenerative diseases and neuropsychiatric disorders.},
  year = {2025},
  journal = {Nature Reviews Bioengineering},
  pages = {1-22},
  month = {2025-10-13},
  issn = {2731-6092},
  url = {https://www.nature.com/articles/s44222-025-00355-w},
  doi = {10.1038/s44222-025-00355-w},
  language = {en},
}