Recruitment and therapeutic application of macrophages in skeletal muscles after hind limb ischemia.
Recruitment and therapeutic application of macrophages in skeletal muscles after hind limb ischemia.
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DOI：
10.1016/j.jvs.2017.04.070
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发表时间：
2018-06
影响因子：
4.3
通讯作者：
Farrar RP
中科院分区：
文献类型：
--
作者：
Hsieh PL;Rybalko V;Baker AB;Suggs LJ;Farrar RP
外周动脉疾病不仅可引起局部缺血，还可引起骨骼肌损伤。巨噬细胞（MP）在协调肌肉修复中起着重要作用，然而，单核细胞MP在缺血肌肉中的表型转变尚未得到很好的定义。因此，本研究的目的是检查MP的时间募集，并探讨其对缺血肌肉再生的治疗作用。对C57 BL/6小鼠进行单侧股动脉切除。从缺血肌肉中分离骨髓细胞，使用流式细胞术表征。在损伤后24小时将骨髓来源的MP（2 × 106个细胞）注射到缺血的腓肠肌中。使用激光散斑成像测量血流恢复。通过评估缺血肌肉的收缩力来评价功能结局。组织学分析包括定量肌纤维大小、胶原沉积、炎症和MyoD表达细胞的数量以及毛细血管密度。中性粒细胞和炎性单核细胞-MP在损伤后第1天出现。然后，从第5天到第21天，随着再生纤维的观察，成熟的MP作为优势群体保持升高。功能测量结果显示，促炎性M1 MP治疗后，力产生显著增强（94.9% vs 77.9%; P < .05），这与肌纤维尺寸、毛细血管纤维比和灌注增加一致（78.6% vs 39.9%; P < .05）。此外，MyoD表达细胞核的百分比在第4天显著更高，表明M1 MP可能加速肌肉修复。尽管抗炎M2 MP的早期递送改善了肌纤维尺寸，但这伴随着持续的纤维化，表明正在进行的组织重塑，并且观察到较低的力产生。我们证明了缺血性损伤后骨骼肌中骨髓细胞的动力学，并且以时间协调的方式施用外源性M1 MP成功地改善了血管生成和骨骼肌再生。我们的研究结果表明，使用MP的细胞疗法可能是一种有前途的外周动脉疾病的连续治疗方法。许多患有外周动脉疾病的患者肌肉尺寸减小，力量降低，行走能力受损，这极大地影响了他们的生活质量。不幸的是，晚期心血管疾病患者的有效治疗选择有限。因此，我们的目的是检查肌内施用巨噬细胞对血管生成以及肌肉恢复的功效。本研究的结果可作为临床前知识来指导细胞治疗的发展和促进缺血性肌肉再生。
Peripheral arterial disease can cause not only ischemia but also skeletal muscle damage. It has been known that macrophages (MPs) play an important role in coordinating muscle repair; however, phenotype transition of monocyte-MP in ischemic muscle has not been well defined. Hence, the purpose of this study was to examine the temporal recruitment of MPs and to explore their therapeutic effect on ischemic muscle regeneration. Unilateral femoral artery excision was performed on C57BL/6 mice. Myeloid cells were isolated from the ischemic muscles, characterized using flow cytometry. Bone marrow-derived MPs were injected (2 × 106 cells) into the ischemic gastrocnemius muscle 24 hours after injury. Blood flow recovery was measured using laser speckle imaging. Functional outcome was evaluated by assessing the contractile force of ischemic muscles. Histologic analysis included quantification of myofiber size, collagen deposition, number of inflammatory and MyoD-expressing cells, and capillary density. Neutrophils and inflammatory monocytes-MPs were present at day 1 after injury. The mature MPs then remained elevated as the dominant population from day 5 to day 21 with the observation of regenerating fibers. Functional measurements revealed that the force production was significantly enhanced after treatment with proinflammatory M1 MPs (94.9% vs 77.9%; P < .05), and this was consistent with increased myofiber size, capillary-fiber ratio, and perfusion (78.6% vs 39.9%; P < .05). Moreover, the percentage of MyoD-expressing nuclei was significantly higher at day 4, indicating that M1 MPs may hasten muscle repair. Whereas early delivery of anti-inflammatory M2 MPs improved myofiber size, this was accompanied by persistent fibrosis suggesting ongoing tissue remodeling, and lower force production was observed. We demonstrated the dynamics of myeloid cells in skeletal muscle after ischemic insult, and the administration of exogenous M1 MPs in a temporally coordinated manner successfully improved angiogenesis and skeletal muscle regeneration. Our results suggested that cell therapy using MPs may be a promising adjunctive therapeutic approach for peripheral arterial disease. Many patients with peripheral arterial disease have reduced muscle size, reduced strength, and impaired walking ability, which greatly affect their quality of life. Unfortunately, effective therapeutic options for patients with advanced cardiovascular disease are limited. Therefore, we aimed to examine the efficacy of intramuscular administration of macrophages on angiogenesis as well as muscle recovery. Results from this study can be used as preclinical knowledge to guide the development of cell therapy and to enhance ischemic muscle regeneration.
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影响因子：
4.4
作者：
Martinez, Fernando O.;Gordon, Siamon;Mantovani, Alberto
通讯作者：
Mantovani, Alberto
影响因子：
20.1
作者：
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通讯作者：
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影响因子：
0.7
作者：
Nucera, Silvia;Biziato, Daniela;De Palma, Michele
通讯作者：
De Palma, Michele
DOI：
10.1152/ajpheart.00004.2011
发表时间：
2011-06-01
影响因子：
4.8
作者：
Peng, XinZhi;Wang, Jinsong;Burnett, Mary Susan
通讯作者：
Burnett, Mary Susan
影响因子：
4.9
作者：
Mann CJ;Perdiguero E;Kharraz Y;Aguilar S;Pessina P;Serrano AL;Muñoz-Cánoves P
通讯作者：
Muñoz-Cánoves P