Kim Do Jung, Youn Young-Nam, Kim Ji Min, Lim Sang-Hyun
Department of Thoracic and Cardiovascular Surgery, Ajou University Medical Center, Ajou University School of Medicine, Suwon, Republic of Korea.
Department of Medicine, The Graduate School of Yonsei University, Seoul, Republic of Korea.
Sci Rep. 2025 Jul 1;15(1):20397. doi: 10.1038/s41598-025-08283-w.
In critical limb-threatening ischemia (CLTI), failed revascularization and pharmacotherapy substantially increase amputation and mortality risks. Mesenchymal stem cells (MSCs) are a promising therapeutic option for CLTI. This study evaluated the therapeutic effects of embryonic stem cell-derived MSCs (E-MSCs) on inflammation and angiogenesis under ischemic conditions across different E-MSC doses. Hindlimb ischemia was induced in 85 BALB/c nude mice by cauterizing the femoral and branched arteries. The mice were divided into five groups: non-ischemia (G1); saline-treated ischemia (G2); and ischemia treated with E-MSCs at low, medium, and high doses (G3-G5). Therapeutic effects were assessed using the rotarod test, blood perfusion ratio, and histological and cytokine analyses. G1 exhibited normal blood perfusion and motor function, whereas E-MSC-treated groups (G3-G5) demonstrated improved perfusion compared to G2. Although the medium-dose group (G4) showed numerically greater recovery, differences between G3, G4, and G5 were not statistically significant, suggesting no dose-response. All E-MSC-treated groups exhibited reduced inflammation and increases in motor function and angiogenic factors. Histological analysis revealed enhanced myofiber regeneration, reduced inflammatory infiltration, and diminished collagen deposition in the ischemic muscle of G3-G5. These changes were observed across all dose groups without significant dose-dependent differences. These results suggest E-MSCs enhance blood perfusion and modulate inflammation and angiogenesis in ischemic limbs, regardless of dose. These findings support the therapeutic potential of E-MSCs in CLTI, although further investigation is needed to optimize dosing and elucidate the mechanisms involved.
在严重肢体缺血（CLTI）中，血管重建失败和药物治疗会大幅增加截肢和死亡风险。间充质干细胞（MSCs）是CLTI一种有前景的治疗选择。本研究评估了胚胎干细胞来源的间充质干细胞（E-MSCs）在不同剂量下对缺血条件下炎症和血管生成的治疗效果。通过烧灼股动脉和分支动脉，在85只BALB/c裸鼠中诱导后肢缺血。将小鼠分为五组：非缺血组（G1）；生理盐水处理的缺血组（G2）；以及低、中、高剂量E-MSCs处理的缺血组（G3-G5）。使用转棒试验、血液灌注率以及组织学和细胞因子分析来评估治疗效果。G1表现出正常的血液灌注和运动功能，而E-MSCs处理组（G3-G5）与G2相比，灌注有所改善。尽管中剂量组（G4）在数值上显示出更大的恢复，但G3、G4和G5之间的差异无统计学意义，表明不存在剂量反应关系。所有E-MSCs处理组均表现出炎症减轻，运动功能和血管生成因子增加。组织学分析显示，G3-G5缺血肌肉中的肌纤维再生增强、炎症浸润减少以及胶原沉积减少。在所有剂量组中均观察到这些变化，且无明显的剂量依赖性差异。这些结果表明，无论剂量如何，E-MSCs均可增强缺血肢体的血液灌注并调节炎症和血管生成。这些发现支持了E-MSCs在CLTI中的治疗潜力，尽管需要进一步研究以优化给药剂量并阐明其中涉及的机制。
