Project R-13264

Human dental pulp stem cells as a patient-in-a-dish model for Charcot-Marie-Tooth disease type 1A (Research)

Charcot-Marie-Tooth disease (CMT) affects 1 in 2500 individuals worldwide and is characterized by progressive damage to the peripheral motor and sensory nerves. The most prevalent disease form, CMT type 1A (CMT1A), is caused by a peripheral myelin protein 22 (PMP22) gene duplication. PMP22 is mainly expressed by Schwann cells, the myelinating cells of the peripheral nervous system. Despite preclinical successes, no cure exists, partly due to the lack of translatable human CMT1A cell culture models. While animal models fail to recapitulate human disease, human Schwann cell isolation is limited by ethical issues and low proliferation rates. Our group has shown that human dental pulp stem cells can differentiate into functional Schwann cells. I will use these cells as a new in vitro model to study CMT1A. DPSC are isolated from wisdom teeth extracted for orthodontic reasons (biological waste) and divide rapidly. Hence, this project is the first to develop a clinically relevant human in vitro model for CMT1A using DPSC, fulfilling an unmet need. First, I will overexpress one PMP22 copy in DPSC to mimic CMT1A. Cells are cultured in upscalable 3D hydrogels and electrospun fibers to evaluate cellular interactions and axonal myelination. These translatable models offer novel insights into CMT1A mechanisms while enabling high-throughput drug screening and are thus of interest to the entire CMT1A research field.

01 November 2022 - 31 October 2026