Chen Junyu, Chen Minghong, Wang Xuerui, Yao Meilian, Chen Jing, Zhang Jian, Long Tianyi
Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China; Center of Coronary Circulation, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Surgery. 2025 Aug;184:109460. doi: 10.1016/j.surg.2025.109460. Epub 2025 Jun 6.
Peripheral artery disease, an age-related ischemic disease, primarily affects the elderly. Cell therapy is a promising treatment for peripheral artery disease. This study aims to investigate the effects of macrophages derived from young mice on neovascularization and recovery in a hindlimb ischemia model of aged mice.
Monocytes were isolated from the bone marrow of young mice and cultured in vitro to generate bone marrow-derived macrophages. After polarization, young-derived M2-like bone marrow-derived macrophages were obtained. Aged mice were divided into 3 groups: saline group, young-derived nonpolarized bone marrow-derived macrophages group, and young-derived M2-like bone marrow-derived macrophages group. Hindlimb ischemia was induced in aged mice via femoral artery ligation. Three days after surgery, saline, young-derived nonpolarized bone marrow-derived macrophages, or young-derived M2-like bone marrow-derived macrophages were intramuscularly injected into the ischemic hindlimb. Doppler imaging, ischemia and mobility scores, and histological analysis were used to assess blood flow, functional recovery, and tissue repair. Neovascularization was further evaluated using micro-computed tomography and immunofluorescence staining.
Compared with the saline group, aged mice in the young-derived M2-like bone marrow-derived macrophages group exhibited notable blood flow recovery, along with corresponding improvements in tissue and functional recovery. In addition, in terms of neovascularization, the young-derived M2-like bone marrow-derived macrophages group demonstrated a richer vascular bed, with significant increases in both arteriogenesis and angiogenesis, as well as enhanced endothelial cell function.
M2-like macrophages derived from young mice enhance neovascularization of aged mice with ischemia, leading to improved blood perfusion and tissue functional recovery. This suggests that macrophages represent a promising new therapeutic strategy for peripheral artery disease in the elderly.
外周动脉疾病是一种与年龄相关的缺血性疾病，主要影响老年人。细胞治疗是外周动脉疾病的一种有前景的治疗方法。本研究旨在探讨年轻小鼠来源的巨噬细胞对老年小鼠后肢缺血模型中新血管形成和恢复的影响。
从小鼠骨髓中分离单核细胞并在体外培养以生成骨髓来源的巨噬细胞。极化后，获得年轻来源的M2样骨髓来源的巨噬细胞。将老年小鼠分为3组：生理盐水组、年轻来源的未极化骨髓来源的巨噬细胞组和年轻来源的M2样骨髓来源的巨噬细胞组。通过股动脉结扎诱导老年小鼠后肢缺血。手术后3天，将生理盐水、年轻来源的未极化骨髓来源的巨噬细胞或年轻来源的M2样骨髓来源的巨噬细胞肌肉注射到缺血后肢。使用多普勒成像、缺血和活动评分以及组织学分析来评估血流、功能恢复和组织修复。使用微型计算机断层扫描和免疫荧光染色进一步评估新血管形成。
与生理盐水组相比，年轻来源的M2样骨髓来源的巨噬细胞组的老年小鼠表现出明显的血流恢复，同时组织和功能恢复也相应改善。此外，在新血管形成方面，年轻来源的M2样骨髓来源的巨噬细胞组显示出更丰富的血管床，动脉生成和血管生成均显著增加，内皮细胞功能也增强。
年轻小鼠来源的M2样巨噬细胞可增强老年缺血小鼠的新血管形成，从而改善血液灌注和组织功能恢复。这表明巨噬细胞是老年外周动脉疾病一种有前景的新治疗策略。
