嗅上皮干细胞在嗅觉功能调控与再生修复中的研究进展

Research advances in olfactory epithelial stem cells in the regulation of olfactory function and regenerative repair

摘要:

嗅觉功能障碍是一种普遍存在并严重影响生活质量的健康问题，其临床治疗仍面临重大挑战。作为嗅觉系统的核心再生引擎，嗅上皮干细胞，包括水平基底细胞和球状基底细胞，通过精确的稳态调控，维持嗅觉感觉神经元（OSNs）的持续再生。本综述系统梳理了生理状态下与病理微环境中嗅上皮干细胞的分子调控网络，解析Notch、Wnt、成纤维细胞生长因子（FGF）和骨形态发生蛋白（BMP）信号通路在嗅上皮干细胞增殖与分化调控中的作用，探究其如何驱动嗅上皮干细胞增殖、更新、分化，维持其存活并提供微环境支持，同时深入剖析了急性损伤、慢性炎症及衰老等相关嗅觉功能障碍的差异化病理机制。在此基础上，本综述进一步探讨了基于干细胞移植的创新治疗策略、难点以及未来发展方向，为后续嗅觉功能障碍精准干预的基础研究与临床试验设计提供参考。

Abstract:

Olfactory dysfunction is a widespread health problem that seriously damages the quality of life, and its clinical treatment is still facing major challenges. As the core regeneration engine of the olfactory system, olfactory epithelial stem cells, including horizontal basal cells and globose basal cells, maintain the continuous regeneration of olfactory sensory neurons (OSNs) through precise homeostatic regulation. This paper systematically reviews the molecular regulatory networks of olfactory epithelial stem cells in both physiological and pathological microenvironments. It elucidates the roles of the Notch, Wnt, FGF, and BMP signaling pathways in the proliferation and differentiation of olfactory epithelial stem cells, and explores how they drive the proliferation, renewal and differentiation of olfactory epithelium, maintain survival and microenvironment support. It also provides an in-depth analysis of the distinct pathological mechanisms of olfactory dysfunction related to acute injury, chronic inflammation, and aging-related olfactory impairments. On this basis, we further discussed the current difficulties and future development of innovative treatment strategies based on stem cell transplantation, which may provide a reference for basic research and clinical trial design of precise intervention of olfactory dysfunction.