海拔相关环境因素对骨髓间充质干细胞生物学行为影响的研究进展

Research Progress on the Effects of Altitude-Related Environmental Factors on the Biological Behavior of Bone Marrow Mesenchymal Stem Cells

摘要: 骨髓间充质干细胞(bone marrow mesenchymal stem cells, BMSCs)是一类来源于中胚层、具有自我更新能力和多向分化潜能的成体干细胞，可分化为成骨细胞、软骨细胞、脂肪细胞及其他多种间质来源细胞，并在组织修复、免疫调节和再生医学中具有重要应用价值。BMSCs的生物学行为高度依赖其所处微环境，外界环境变化可显著影响其增殖、迁移、分化、旁分泌及存活能力。随着海拔升高，局部环境中氧分压降低、温度下降、紫外线辐射增强以及重力负荷条件变化等因素共同作用，可对BMSCs的功能状态产生复杂影响。现有研究表明，缺氧可在一定范围内增强BMSCs的增殖、迁移、成骨与软骨分化潜能，并改善其旁分泌和促血管生成能力；低温则多表现为抑制细胞代谢、增殖和部分分化功能，但可提高细胞对不良环境的耐受性；紫外线对BMSCs的影响具有剂量依赖性，低剂量暴露对基本表型影响有限，而较高剂量可能影响其迁移、黏附及衰老进程；重力减低或模拟微重力可通过重塑细胞骨架和调控干性相关信号通路，改变BMSCs的分化方向及成骨潜能。本文围绕海拔升高所伴随的主要环境变化，系统综述其对BMSCs生物学特性的影响，以期为高海拔环境下干细胞生物学研究及再生医学应用提供参考。

Abstract: Bone marrow mesenchymal stem cells (BMSCs) are adult stem cells of mesodermal origin with self-renewal capacity and multipotent differentiation potential. They can differentiate into osteoblasts, chondrocytes, adipocytes, and various other mesenchymal lineage cells, making them highly valuable in tissue repair, immunoregulation, and regenerative medicine. The biological behavior of BMSCs is highly dependent on their microenvironment, and changes in external conditions can significantly influence their proliferation, migration, differentiation, paracrine activity, and survival. At high altitudes, multiple environmental factors—including reduced oxygen pressure, lower temperatures, increased ultraviolet (UV) radiation, and altered gravitational load—interact to produce complex effects on BMSC function. Current studies indicate that hypoxia can, within certain limits, enhance BMSC proliferation, migration, osteogenic and chondrogenic differentiation, as well as improve paracrine function and pro-angiogenic capacity. Low temperatures generally suppress cellular metabolism, proliferation, and certain differentiation functions but may increase tolerance to adverse conditions. UV exposure exhibits dose-dependent effects: low doses minimally affect basic phenotypes, whereas higher doses can impact migration, adhesion, and cellular senescence. Reduced gravity or simulated microgravity can remodel the cytoskeleton and regulate stemness-related signaling pathways, altering differentiation patterns and osteogenic potential. This review systematically summarizes the effects of high-altitude environmental factors on BMSC biological characteristics, aiming to provide insights for stem cell research and regenerative medicine applications in high-altitude conditions.