(T1305) Phenotypic and transcriptomic characterization of human induced pluripotent stem cell-derived Schwann cells/Schwann cell precursors for peripheral nerve regeneration
Research Associate The Chinese University of Hong Kong (CUHK), Hong Kong
Abstract: Peripheral nerve injury (PNI), a common form of peripheral neuropathy, is a widespread and debilitating health problem that affects millions of patients globally. Despite the limited nerve regenerative capacity of peripheral nerves and current advances made in nerve reconstruction, a majority of patients with PNI does not regain satisfactory functions after surgical intervention. Limitations have also been found in current surgical approaches for PNI, and therefore, new therapeutic strategies are urgently required to improve not only the treatment outcomes but also the quality of patients’ lives. Schwann cells (SCs) are the most abundant glial cells of the peripheral nervous system and are crucial for axon growth, neuronal support, and nerve repair. They and their precursors (i.e. Schwann cell precursors SCPs) are considered potential cell types for embedding into nerve guidance conduits for transplantation to promote nerve regeneration after PNI. However, sources of human autologous SCs/SCPs are limited. Here, we presented an induction strategy for generating a stable source of functional SCs/SCPs from human induced pluripotent stem cells (hiPSCs) for incorporation to nerve guidance conduits. A combination of phenotypic assays and single-cell RNA sequencing (scRNA-seq) analyses of induced SCs/SCPs enabled comprehensive classification and understanding of the cellular profiles and transcriptomes of hiPSC-derived SC/SCP subtypes. Our study provided evidence for the robust induction of functional SCs/SCPs and demonstrated the important roles of different biological and biophysical cues provided by SCs/SCPs for peripheral nerve regeneration. These cell types may serve as therapeutic tools to improve iPSC-based therapies for peripheral neuropathy.
Funding Source: The work was supported by the General Research Fund (Ref.: 14120522 and 14118818) from the Research Grants Council , and the research fund from Health@InnoHK program by the Government of Hong Kong Special Administrative Region, China.
