Autologous culture-modified mononuclear cells confer vascular protection after arterial injury

Autologous culture-modified mononuclear cells confer vascular protection after arterial injury
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DOI:
10.1161/01.cir.0000089084.48655.49
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发表时间:
2003-09-23
期刊:
影响因子:
37.8
通讯作者:
Simari, RD
Simari, RD
中科院分区:
医学1区
文献类型:
--
作者:
Gulati, R;Jevremovic, D;Simari, RD

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骨髓来源的细胞已被证明有助于血管损伤后的内皮替代。外周血单个核细胞体外培养产生具有内皮细胞表型特征的细胞。为了检验将自体培养修饰的单核细胞(CMMCs)递送至损伤的动脉可以减弱血管对损伤的反应的假设,研究了兔模型。方法和结果-将兔外周血单核细胞在内皮生长培养基中培养7至12天,产生具有不同内皮表型的高度增殖细胞(表达CD 31和内皮一氧化氮合酶并能够吸收乙酰化LDL)。使用球囊颈动脉损伤的兔模型来评估第7天CMMC递送对血管反应的影响。动物经历球囊损伤并通过20分钟的局部停留立即递送自体CMMC或缓冲盐水。分娩后4周,在所有血管层中检测到标记的CMMCs。还鉴定了定位于管腔并针对内皮标记物染色的细胞集落。与生理盐水相比,在球囊损伤时局部给予CMMC在4周时加速了再内皮化(P
Background-Bone marrow-derived cells have been shown to contribute to endothelial replacement after vascular injury. In vitro culture of peripheral blood mononuclear cells produces cells with phenotypic characteristics of endothelium. To test the hypothesis that delivery of autologous culture-modified mononuclear cells (CMMCs) to injured arteries could attenuate the vascular response to injury, a rabbit model was studied.Methods and Results-Rabbit peripheral blood mononuclear cells were cultured in endothelial growth media for 7 to 12 days, yielding highly proliferative cells with distinct endothelial phenotype (expressing CD31 and endothelial nitric oxide synthase and capable of acetylated LDL uptake). A rabbit model of balloon carotid injury was used to evaluate the effect of day 7 CMMC delivery on vascular responses. Animals underwent balloon injury and immediate delivery of autologous CMMCs or buffered saline by 20 minutes of local dwelling. Fluorescence-labeled CMMCs were detected in all vessel layers 4 weeks after delivery. Colonies of cells that localized to the lumen and stained for endothelial markers were also identified. Local CMMC administration at the time of balloon injury accelerated reendothelialization at 4 weeks compared with saline (P