Patient-Derived Stem Cells, Another in vitro Model, or the Missing Link Toward Novel Therapies for Autism Spectrum Disorders?

Autism Spectrum Disorders (ASDs) is a multigenic and multifactorial neurodevelopmental group of disorders diagnosed in early childhood, leading to deficits in social interaction, verbal and non-verbal communication and characterized by restricted and repetitive behaviors and interests. To date, genetic, descriptive and mechanistic aspects of the ASDs have been investigated using mouse models and post-mortem brain tissue. More recently, the technology to generate stem cells from patients' samples has brought a new avenue for modeling ASD through 2D and 3D neuronal models that are derived from a patient's own cells, with the goal of building new therapeutic strategies for treating ASDs. This review analyses how studies performed on mouse models and human samples can complement each other, advancing our current knowledge into the pathophysiology of the ASDs. Regardless of the genetic and phenotypic heterogeneities of ASDs, convergent information regarding the molecular and cellular mechanisms involved in these disorders can be extracted from these models. Thus, considering the complexities of these disorders, patient-derived models have immense potential to elucidate molecular deregulations that contributed to the different autistic phenotypes. Through these direct investigations with the human in vitro models, they offer the potential for opening new therapeutic avenues that can be translated into the clinic.