Pathological Analysis of Cell Differentiation in Cholesterol Granulomas Experimentally Induced in Mice.
Pathological Analysis of Cell Differentiation in Cholesterol Granulomas Experimentally Induced in Mice.
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DOI：
10.7150/ijms.13853
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发表时间：
2016
影响因子：
3.6
通讯作者：
Kawakami T
中科院分区：
文献类型：
--
作者：
Sakai K;Nakano K;Matsuda S;Tsujigiwa H;Ochiai T;Shoumura M;Osuga N;Hasegawa H;Kawakami T
本研究将胆固醇植入小鼠皮下组织，诱导胆固醇肉芽肿形成。进行组织学检查以确定细胞的类型和来源。在6个月内对包埋的胆固醇周围组织进行组织学检查。使用ddY小鼠和GFP骨髓移植小鼠研究胆固醇肉芽肿中的细胞分化。将胆固醇包埋在小鼠皮下，并在6个月的时间内进行组织病理学检查。结果表明，在2周时，胆固醇部分被肉芽组织所取代。肉芽组织以巨噬细胞和异物巨细胞为主，中央有少量成纤维细胞、胶原纤维和毛细血管。与2周相比，3个月时观察到更多的肉芽组织。观察到类似的细胞，然而，与2周相比，存在更多的成纤维细胞、胶原束和毛细血管。在6个月时，胆固醇大部分被主要由成纤维细胞和胶原纤维组成的纤维组织以及一些巨噬细胞和异物巨细胞取代。具体地，组织的外部部分由成纤维细胞、胶原束和毛细血管组成，并且内部部分填充有胶原束。免疫组化结果显示，巨噬细胞和异物巨细胞呈GFP和CD68阳性，而胆固醇肉芽肿外部的成纤维细胞和毛细血管呈GFP阴性。一些梭形成纤维细胞也呈GFP阳性。免疫荧光双重染色显示，血管内衬细胞对GFP和CD 31均呈阳性，表明这些细胞是内皮细胞，实际上来源于移植的骨髓细胞。结果提示，巨噬细胞、异物巨细胞、成纤维细胞和毛细血管内皮细胞均为骨髓源性间充质细胞。
In this study, cholesterin was implanted in the subcutaneous tissue in mice to induce the formation of cholesterol granuloma. Histological examination was carried out to determine the type and source of cells. The tissue surrounding the embedded cholesterin was examined histologically within the period of 6 months. Cell differentiation in cholesterol granulomas was investigated using ddY mice and GFP bone marrow transplanted mice. Cholesterin was embedded in mice subcutaneously and histopathological examination was carried out in a period of 6 months. Results showed that at 2 weeks, cholesterin was replaced partly by granulation tissues. The majority of cells in the granulation tissues were macrophages and foreign body giant cells and the center consists of small amount of fibroblasts, collagen fibers and capillaries. At 3 months, more granulation tissue was observed compared to 2 weeks. Similar cells were observed, however, there were more fibroblasts, collagen bundles and capillaries present compared to 2 weeks. At 6 months, the cholesterin was mostly substituted by fibrous tissues consisting mainly of fibroblasts and collagen fibers with some macrophages and foreign body giant cells. Specifically, the outer part of the tissue consists of fibroblasts, collagen bundles and capillaries and the inner portion is filled with collagen bundles. Immunohistochemistry revealed that macrophages and foreign body giant cells were positive to GFP and CD68 although the fibroblasts and capillaries in the outer portion of cholesterol granulomas were GFP negative. Some spindle shape fibroblasts were also GFP positive. Immunofluorescent double staining revealed that cells lining the blood vessels were both positive to GFP and CD31 indicating that those were endothelial cells and were actually derived from the transplanted bone marrow cells. The results suggest that macrophages, foreign body giant cells as well as fibroblasts and capillary endothelial cells are bone marrow derived mesenchymal cells.