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首页> 外文期刊>JACC. Cardiovascular imaging. >Molecular imaging of bone marrow mononuclear cell survival and homing in murine peripheral artery disease
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Molecular imaging of bone marrow mononuclear cell survival and homing in murine peripheral artery disease

机译：鼠外周动脉疾病中骨髓单个核细胞存活和归巢的分子成像

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This study aims to provide insight into cellular kinetics using molecular imaging after different transplantation methods of bone marrowderived mononuclear cells (MNCs) in a mouse model of peripheral artery disease (PAD). MNC therapy is a promising treatment for PAD. Although clinical translation has already been established, there is a lack of knowledge about cell behavior after transplantation and about the mechanism whereby MNC therapy might ameliorate complaints of PAD. MNCs were isolated from F6 transgenic mice (FVB background) that express firefly luciferase (Fluc) and green fluorescence protein (GFP). Male FVB and C57Bl6 mice (n = 50) underwent femoral artery ligation and were randomized into 4 groups receiving the following: 1) single intramuscular (IM) injection of 2 × 10 6 MNCs; 2) 4 weekly IM injections of 5 × 10 5 MNCs; 3) 2 × 10 6 MNCs intravenously; and 4) phosphate-buffered saline as control. Cells were characterized by flow cytometry and in vitro bioluminescence imaging (BLI). Cell survival, proliferation, and migration were monitored by in vivo BLI, which was validated by ex vivo BLI, post-mortem immunohistochemistry, and flow cytometry. Paw perfusion and neovascularization was measured with laser Doppler perfusion imaging (LDPI) and histology, respectively. In vivo BLI revealed near-complete donor cell death 4 weeks after IM transplantation. After intravenous transplantation, BLI revealed that cells migrated to the injured area in the limb, as well as to the liver, spleen, and bone marrow. Ex vivo BLI showed presence of MNCs in the scar tissue and adductor muscle. However, no significant effects on neovascularization were observed, as monitored by LDPI and histology. This is one of the first studies to assess kinetics of transplanted MNCs in PAD using in vivo molecular imaging. MNC survival is short-lived, MNCs do not preferentially home to injured areas, and MNCs do not significantly stimulate perfusion in this particular model.
机译：这项研究的目的是在外周动脉疾病（PAD）小鼠模型中采用不同的骨髓源性单核细胞（MNCs）移植方法后，利用分子成像技术深入了解细胞动力学。 MNC疗法是用于PAD的有前途的疗法。尽管已经建立了临床翻译方法，但缺乏有关移植后细胞行为以及MNC治疗可能改善PAD症状的机制的知识。从表达萤火虫荧光素酶（Fluc）和绿色荧光蛋白（GFP）的F6转基因小鼠（FVB背景）中分离出MNC。雄性FVB和C57B16小鼠（n = 50）进行了股动脉结扎，并随机分为4组，分别接受以下治疗：1）单次肌内（IM）注射2×10 6个MNC; 2）每周4次IM注入5×10 5个MNC; 3）静脉注射2×10 6个跨国公司; 4）磷酸盐缓冲盐水作为对照。通过流式细胞仪和体外生物发光成像（BLI）表征细胞。细胞存活，增殖和迁移通过体内BLI进行监测，并通过离体BLI，验尸后的免疫组织化学和流式细胞仪进行验证。分别用激光多普勒灌注成像（LDPI）和组织学测量爪的灌注和新生血管形成。 IM移植后4周，体内BLI显示供体细胞几乎完全死亡。静脉移植后，BLI显示细胞迁移到肢体的受损区域，以及肝，脾和骨髓。体外BLI显示疤痕组织和内收肌中存在MNC。然而，如通过LDPI和组织学监测的，未观察到对新血管形成的显着影响。这是使用体内分子成像技术评估PAD中移植的MNC动力学的首批研究之一。 MNC的生存期很短，MNC不会优先将其放置在受伤区域，并且MNC在这种特定模型中不会显着刺激灌注。

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