The 2020s Tooth Fairy: from loose tooth to neuronal cell cultures, an innovative method for in vitro genetic disease modeling of a rare neurological disorder

The development of adequate in vitro disease models is a major issue in Biomedical Genetics. Those models allow for the initial screening of novel therapeutics and help us get an insight on the cellular mechanisms that underly pathology in each case. In fact, one of the best ways to get those insights is the analysis of patient-derived cells. Yet, not every cell holds potential to recapitulate relevant disease features. For neurodegenerative diseases in particular, it is challenging to grow neuronal cultures that accurately represent them because of the obvious inability to access live neurons. This scenario changed significantly when induced pluripotent stem cells (iPSC) were first described. From then on several differentiation protocols to generate neurons from iPSC were developed. Still, iPSC generation is a laborious/expensive protocol with significant limitations in terms of production and subsequent uses. Here we present an alternative to establish patient-derived neuronal cells in a much more expedite way. We are taking advantage of the existence of a population of multipotent stem cells (SC) in human dental pulp, the dental pulp stem cells (DPSC), to establish mixed neuronal and glial cultures for a rare neurological genetic disorder: the Sanfilippo syndrome. Sanfilippo-derived DPSC have never been used for differentiation into specific cell types even though they represent a natural source of SC that may be used to investigate human disease especially for the infantile forms. This is a total innovation in the field and we believe it holds potential to set a new trend for investigating the cellular/gene expression changes that occur in Sanfilippo and other related diseases as it relies on a non-invasive, cost-effective approach that can be set as a routine in any lab with standard cell culture conditions. Ultimately, the same method may be applied for virtually any monogenic disorder with neurological presentation.