Bone marrow-derived progenitor cells contribute to experimental choroidal neovascularization
Bone marrow-derived progenitor cells contribute to experimental choroidal neovascularization
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DOI：
10.1167/iovs.03-0371
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发表时间：
2003-11-01
影响因子：
4.4
通讯作者：
Cousins, SW
中科院分区：
文献类型：
--
作者：
Espinosa-Heidmann, DG;Caicedo, A;Cousins, SW
目的。脉络膜新生血管（CNV）的发病机制被认为是由血管生成驱动的，在这一过程中，新血管复合体的细胞成分来自于邻近已存在的毛细血管中的细胞。最近，另一种被称为出生后血管发生的范式被证明有助于某些形式的新生血管形成。在血管发生中，新血管复合体的细胞成分来源于骨髓中的循环血管祖细胞。本研究将绿色荧光蛋白（GFP）标记的骨髓移植与激光诱导的CNV相结合，研究血管发生对CNV形成的贡献。10只成年C57BL/6雌性小鼠作为骨髓移植受体。从3只转β -肌动蛋白启动子GFP的C57BL/6雌性小鼠获得骨髓。骨髓移植1个月后，用红色二极管激光在受体小鼠的每只眼睛的脉络膜上制造4个单独的肿块，诱导CNV。CNV诱导4周后，对受体小鼠的眼睛进行免疫组化处理，检测血管平滑肌细胞（α -平滑肌肌动蛋白、desmin和NG2硫酸软骨素蛋白多糖）、内皮细胞（CD31、BS-1凝集素）或巨噬细胞（F4/80）的GFP和标志物。gfp标记的细胞占病变细胞总数的17%。许多gfp标记的细胞对α -平滑肌肌动蛋白（39%）、desmin、NG2、CD31（41%）、BS-1凝集素或F4/80有免疫反应。gfp标记的细胞在形态学上与通常存在于CNV病变中的细胞难以区分。本研究首次证实骨髓源性祖细胞是CNV中内皮细胞和平滑肌样细胞的来源。
PURPOSE. The pathogenesis of choroidal neovascularization (CNV) is postulated to be driven by angiogenesis, a process in which the cellular components of the new vessel complex are derived from cells resident within an adjacent preexisting capillary. Recently, an alternative paradigm, termed postnatal vasculogenesis, has been shown to contribute to some forms of neovascularization. In vasculogenesis,the cellular components of the new vessel complex are derived from circulating vascular progenitors from bone marrow. In the current study, transplantation of green fluorescent protein (GFP)-labeled bone marrow and laser-induced CNV were combined to examine the contribution of vasculogenesis to the formation of CNV.METHODS. Ten adult C57BL/6 female mice were used as recipients for bone marrow transplantation. Bone marrow was obtained from three C57BL/6 female mice transgenic for the beta-actin promoter GFP. One month after bone marrow transplantation, CNV was induced in recipient mice by making four separate bums in the choroid of each eye with a red diode laser. Four weeks after CNV was induced, eyes of recipient mice were processed for immunohistochemistry to detect GFP and markers for vascular smooth muscle cells (alpha-smooth muscle actin, desmin, and NG2 chondroitin sulfate proteoglycan), endothelial cells (CD31, BS-1 lectin), or macrophages (F4/80).RESULTS. GFP-labeled cells represented 17% of the total cell population in the lesion. Many of the GFP-labeled cells were immunoreactive for alpha-smooth muscle actin (39%), desmin, NG2, CD31 (41%), BS-1 lectin, or F4/80. GFP-labeled cells were morphologically indistinguishable from cells, normally present in CNV lesions.CONCLUSIONS. This study is the first to demonstrate that bone marrow-derived progenitor cells are a source of endothelial and smooth musclelike cells in CNV.