Pluripotent stem cells-derived Schwann cells: an innovative strategy for trigeminal neuralgia?

Dear Editor, We were intrigued to read the study by Wei et al.1 titled ‘In situ tissue profile of rat trigeminal nerve in trigeminal neuralgia using spatial transcriptome sequencing.’ In this study, the authors simultaneously observed demyelination and remyelination of Schwann cells in the trigeminal nerve of trigeminal neuralgia (TN) model mice. Furthermore, they noted that various ligand–receptor interactions in the trigeminal ganglion could influence these processes1. TN is described as sudden, typically unilateral, severe, and brief stabbing pain attacks in one or more branches of the trigeminal nerve. Although the exact cause is not fully understood, as the authors mentioned, demyelination of primary sensory afferent nerves at the trigeminal root entry zone is considered one of the main pathophysiological mechanisms of TN2. It is worth noting that all current clinical treatments are not universally effective, with issues such as unstable treatment effects, potential complications, and high recurrence rates1. Developing innovative, more effective treatment strategies targeting demyelination of the trigeminal nerve is a shared goal for both the authors and us. Spontaneous remyelination has been proven to be highly effective in the early stages of demyelinating disease animal models, preventing axonal degeneration and supporting long-term neuronal survival3. However, unfortunately, spontaneous remyelination often fails in demyelinating lesions. In such cases, transplanting exogenous Schwann cells may be a suitable option for treating various diseases caused by demyelination, including TN. However, the amplification of Schwann cells harvested from human nerves is a lengthy and low-yield process. Additionally, these cells are heterogeneous and easily influenced by culture conditions. Improving these issues with human-derived Schwann cells through novel strategies could accelerate both basic research and clinical practice in the treatment of demyelinating diseases (including TN). Pluripotent stem cells (PSCs) are a type of versatile cells capable of unlimited proliferation and differentiation into all three germ layers, generally including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Recent studies have successfully differentiated PSCs into Schwann cells or oligodendrocyte precursor cells (OPCs), which, along with their derivatives, possess the ability to form myelin sheaths4. Although the current mechanisms and clues remain unclear, OPCs, which are inconsistent with the embryonic development origin of Schwann cells, may also serve as a source of Schwann cells. In 2023, Feng et al.5 utilized CRISPR/Cas9 technology to successfully construct low-immunogenic iPSC-derived OPCs, providing readily available and direct donor cells for a wide range of demyelinating diseases. Although there is currently no direct evidence supporting the efficacy of Schwann cells derived from PSCs for TN, Schwann cells/OPCs from different sources have demonstrated significant therapeutic potential in other demyelinating disorders or neurological diseases, including spinal cord demyelination, spinal cord injury, and multiple sclerosis. In summary, we greatly appreciate and commend the work of Wei et al.1. Based on the spatial transcriptome sequencing evidence of trigeminal neuralgia they provided and our summarized relevant knowledge, we recommend future research to explore the therapeutic potential of PSC-derived Schwann cells in trigeminal neuralgia through basic research endeavors. Ethical approval Not applicable. Consent Not applicable. Source of funding This research was supported by the Beijing Shunyi District Research and Development Program, Award Number: Shunyi2023Q06. Author contribution W.S. and J.W.: conceptualization; K.H.: funding acquisition. All authors were involved in the writing – original draft and writing – review and editing. Conflicts of interest disclosure Author Jian Wang is employed by Allife Medicine Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Research registration unique identifying number (UIN) Not applicable. Guarantor Wenpeng Song and Hao Wang. Data availability statement The dataset supporting the conclusions of this article is included within the article. Provenance and peer review Not commissioned, externally peer-reviewed.