Project R-15966

Engineering a nerve-in-a-dish: microtopography-guided differentiation of dental pulp stem cells for studying Charcot-Marie-Tooth disease. (Research)

Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited peripheral neuropathy, yet, no effective treatment exists, partly due to the lack of relevant human in vitro models. Current human cell-based models primarily use iPSC-derived Schwann-like cells that remain immature and non-functional, not accurately reflecting the pathology. To address this gap, this project pioneers an innovative and interdisciplinary approach using CMT1A patient-derived dental pulp stem cells (DPSC), which are particularly advantageous because they can differentiate into Schwann cells (SCs) and motor neurons (MNs). Notably, the role of MNs in CMT1A has been understudied, despite emerging evidence that they may contribute to the disease pathology. My project aims to engineer a physiologically relevant "nerve-in-a-dish" model based on the use of microtopographies to guide DPSC differentiation into mature SCs and MNs. I will integrate advanced biomaterial engineering and patient-derived cells to (1) optimize DPSC-derived SC and MN differentiation, (2) establish a 3D hydrogel-based "nerve-in-a-dish" co-culture model mimicking SC-MN interactions, and (3) elucidate disease-specific cellular and molecular dysfunctions in CMT1A. This model will serve as a highly innovative tool for understanding CMT1A pathogenesis and enable high-throughput drug screening, bridging the translational gap between preclinical studies and clinical applications.

01 October 2025 - 30 September 2029