Mice that lack the angiogenesis inhibitor, thrombospondin 2, mount an altered foreign body reaction characterized by increased vascularity
Mice that lack the angiogenesis inhibitor, thrombospondin 2, mount an altered foreign body reaction characterized by increased vascularity
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DOI：
10.1073/pnas.96.8.4449
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发表时间：
1999-04-13
影响因子：
11.1
通讯作者：
Bornstein, P
中科院分区：
文献类型：
--
作者：
Kyriakides, TR;Leach, KJ;Bornstein, P
小鼠的血栓反应蛋白2基因(Thbs2)的破坏导致了一种复杂的表型，其主要特征是成纤维细胞、结缔组织和血管的异常。考虑到这一表型，我们认为异物反应(FBR)在TSP2基因缺失的小鼠中可能发生了改变。为了研究TSP2在FBR中的作用，将聚二甲基硅氧烷(PDMS)和氧化聚二甲基硅氧烷(OX-PDMS)盘植入TSP2阴性小鼠和对照组。TSP2缺失的皮肤成纤维细胞和对照皮肤成纤维细胞的体外生长也在这两种类型的圆盘上进行了评估。正常成纤维细胞在两个表面均呈单层生长，但细胞与OX-PDMS的附着较弱，对运动敏感。TSP2缺失的成纤维细胞在两个表面均以聚集体的形式生长，其在OX-PDMS上的附着进一步受损。在植入4周后，两种类型的PDMS在TSP2基因缺失的小鼠和对照组小鼠中都产生了类似的具有胶原膜的FBR，但令人惊讶的是，TSP2基因缺失的小鼠形成的胶原膜比正常小鼠形成的胶原膜更厚、血管更丰富。此外，在突变小鼠的胶囊中观察到了形状异常的胶原纤维。这些观察表明，细胞外基质成分TSP2的存在或不存在可以影响FBR的性质，特别是其血管。因此，当植入装置周围的组织需要血管化时，TSP2的表达可能代表局部抑制措施的分子靶点。
Disruption of the thrombospondin 2 gene (Thbs2) in mice results in a complex phenotype characterized chiefly by abnormalities in fibroblasts, connective tissues, and blood vessels. Consideration of this phenotype suggested to us that the foreign body reaction (FBR) might be altered in thrombospondin 2 (TSP2)-null mice. To investigate the participation of TSP2 in the FBR, polydimethylsiloxane (PDMS) and oxidized PDMS (ox-PDMS) disks were implanted in TSP2-null and control mice. Growth of TSP2-null and control skin fibroblasts in vitro also was evaluated on both types of disks. Normal fibroblasts grew as a monolayer on both surfaces, but attachment of the cells to ox-PDMS was weak and sensitive to movement. TSP2-null fibroblasts grew as aggregates on both surfaces, and their attachment was further compromised on ox-PDMS. After a 4-week implantation period, both types of PDMS elicited a similar FBR with a collagenous capsule in both TSP2-null and control mice, However, strikingly, the collagenous capsule that formed in TSP2-null mice was highly vascularized and thicker than that formed in normal mice. In addition, abnormally shaped collagen fibers were observed in capsules from mutant mice. These observations indicate that the presence or absence of an extracellular matrix component, TSP2, can influence the nature of the FBR, in particular its vascularity. The expression of TSP2 therefore could represent a molecular target for local inhibitory measures when vascularization of the tissue surrounding an implanted device is desired.