高原低氧环境下造血系统适应性重塑失调是高原红细胞增多症（HAPC）的核心原因，传统缺氧诱导因子-促红细胞生成素轴理论难以全面揭示其病理转变机制。最新研究发现，低氧驱动高表达转录因子FOS的多能祖细胞亚群扩增、红系分化偏移并形成低氧造血记忆，同时脾脏巨噬细胞铁死亡致红细胞清除障碍、CD47上调逃逸吞噬，共同推动HAPC发生。遗传与炎症因素加剧个体差异。基于上述病理机制，间充质干细胞疗法可通过稳定造血微环境、抗炎抗氧化、多器官损伤修复及全身氧供改善等多重作用，从病理源头与继发损伤层面发挥治疗价值，但目前仍面临细胞异质性高、靶向归巢不足等应用瓶颈。未来需结合易感基因筛查与干细胞技术优化，推动HAPC防治从对症干预向源头精准调控方向发展。

Dysregulated adaptive remodeling of the hematopoietic system under high-altitude hypoxic conditions constitutes the core cause of high-altitude polycythemia (HAPC), and the classic hypoxia-inducible factor-erythropoietin axis theory fails to fully elucidate the mechanisms underlying its pathological transition. Recent studies have revealed that hypoxia drives the expansion of a multipotent progenitor subset with high expression of transcription factor FOS, shifts lineage differentiation toward erythroid cells and establishes hypoxic hematopoietic memory. At the same time, ferroptosis in splenic macrophages impairs erythrocyte clearance and upregulated CD47 enables red blood cells to evade phagocytosis, with all these processes collectively contributing to HAPC pathogenesis. Genetic and inflammatory factors exacerbate individual variability. Based on the above pathological mechanisms, mesenchymal stem cell therapy delivers therapeutic benefits by stabilizing the hematopoietic microenvironment, relieving inflammation and oxidative stress, repairing multi-organ injuries and improving systemic oxygen supply to target both pathogenic origins and secondary lesions, yet its clinical application is currently restricted by bottlenecks such as severe cellular heterogeneity and inadequate targeted homing capacity. Therefore, future work should combine susceptibility gene screening with optimized stem cell technologies to advance the prevention and treatment of HAPC from symptomatic intervention toward precise regulation at the source of lesions.