Xiang Ying-Ying, Won Jong-Hwa, Kim Ji-Seok, Baek Kyung-Wan
Department of Physical Education, Gyeongsang National University, Jinju, 52828, Korea.
Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, 52828, Korea.
Stem Cell Rev Rep. 2025 Apr 14. doi: 10.1007/s12015-025-10881-0.
Exercise-conditioned mesenchymal stem cells (MSCs) may modulate immune responses and improve white adipose tissue (WAT) function. While MSCs are known to reduce inflammation, it remains unclear if exercise-stimulated MSCs can improve obesity-related dysfunctions. This study is the first to explore how exercise-conditioned MSCs may influence adipose tissue inflammation and remodeling in the context of obesity. MSCs were isolated from exercised- and sedentary donor mice, then cultured in vitro. After culture, MSCs were assessed for differentiation capacity and cytokine gene expression, including Il10, as indicators of immune modulation. Exercise-conditioned MSCs were then transplanted into obese recipient mice. Following transplantation, immune cell profiles, inflammatory markers, and adipocyte morphology in recipient WAT were analyzed. Flow cytometry was used to quantify macrophage subtypes (pro-inflammatory and anti-inflammatory), and histological analysis was performed to measure changes in adipocyte size. Exercise-activated MSCs showed a ± 35% increase in Il10 expression and a ± 20% enhancement in differentiation capacity compared to controls, indicating improved immunomodulatory potential. In recipient mice, transplantation led to a ± 25% reduction in pro-inflammatory macrophages (CD86 CD206) and a 15% decrease in adipocyte size within WAT. Additionally, WAT in treated mice showed balanced inflammatory profiles and reduced adipose hypertrophy, suggesting restored immune balance and metabolic health. These findings suggest that exercise-modified MSCs exhibit enhanced immunomodulatory and metabolic regulatory properties. This study provides evidence that exercise enhances MSC characteristics, potentially improving their capacity to modulate adipose tissue immune balance and metabolic function in obesity. Exercise-conditioned MSCs may serve as a foundation for future strategies that integrate exercise-induced stem cell modifications to modulate obesity-related metabolic dysfunction.
运动预处理的间充质干细胞（MSCs）可能调节免疫反应并改善白色脂肪组织（WAT）功能。虽然已知MSCs可减轻炎症，但运动刺激的MSCs是否能改善肥胖相关功能障碍仍不清楚。本研究首次探讨运动预处理的MSCs在肥胖背景下如何影响脂肪组织炎症和重塑。从运动和久坐的供体小鼠中分离出MSCs，然后在体外培养。培养后，评估MSCs的分化能力和细胞因子基因表达，包括作为免疫调节指标的Il10。然后将运动预处理的MSCs移植到肥胖受体小鼠中。移植后，分析受体WAT中的免疫细胞谱、炎症标志物和脂肪细胞形态。使用流式细胞术对巨噬细胞亚型（促炎和抗炎）进行定量，并进行组织学分析以测量脂肪细胞大小的变化。与对照组相比，运动激活的MSCs的Il10表达增加了±35%，分化能力增强了±20%，表明免疫调节潜力得到改善。在受体小鼠中，移植导致促炎巨噬细胞（CD86 CD206）减少了±25%，WAT内脂肪细胞大小减少了15%。此外，治疗小鼠的WAT显示出平衡的炎症谱和减少的脂肪肥大，表明免疫平衡和代谢健康得到恢复。这些发现表明，运动修饰的MSCs表现出增强的免疫调节和代谢调节特性。本研究提供了证据，证明运动增强了MSCs的特性，可能提高其调节肥胖中脂肪组织免疫平衡和代谢功能的能力。运动预处理的MSCs可能为未来整合运动诱导的干细胞修饰以调节肥胖相关代谢功能障碍的策略奠定基础。
