Human Dental Pulp Stem Cells as a Patient-in-a-Dish Model for Charcot-Marie-Tooth Disease Type 1A

Dental pulp stem cells (DPSC) are mesenchymal stem cells residing within the inner mucoid core (dental pulp) of teeth, responsible for tissue turnover and regeneration. Since third molars, or wisdom teeth, are frequently extracted for orthodontic reasons, DPSC are a highly accessible stem cell source. DPSC exhibit high proliferation rates and can be cryopreserved for long periods, rendering them suitable for biobanking. In addition, DPSC are embryonically derived from the neural crest lineage, sharing their origin with myelinating Schwann cells. Hence, we have developed a protocol to differentiate human DPSC towards functional Schwann cells called DPSC-SC. Furthermore, we have implemented these DPSC-SC as a novel research model for Charcot-Marie-Tooth disease type 1A (CMT1A). CMT1A is the most common demyelinating peripheral neuropathy. Previous research has evidenced that CMT1A animal models lack translatability and that human models are necessary to bridge the gap between preclinical and clinical research. We are using human DPSC-SC for CMT1A modeling by mimicking the disease using lentiviral transduction and CRISPR-Cas9 while also building a biobank of patient-derived DPSC-SC.