The application of a murine bone bioreactor as a model of tumor: bone interaction
The application of a murine bone bioreactor as a model of tumor: bone interaction
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DOI：
10.1007/s10585-006-9044-8
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发表时间：
2006-12-01
影响因子：
4
通讯作者：
Holt, Ginger E.
中科院分区：
文献类型：
--
作者：
Halpern, Jennifer;Lynch, Conor C.;Holt, Ginger E.
存在数量有限的体内模型，可以快速评估骨发育或允许在封闭的体内环境中研究肿瘤进展。为了解决这个问题，我们使用骨组织工程技术来产生小鼠体内骨生物反应器。生物反应器是通过将预先加载有盐水作为对照或骨形态发生蛋白-2（BMP-2）的骨传导性羟基磷灰石支架植入到鼠股动脉中来创建的。收获对照和BMP-2生物反应器，并在植入后6周和12周对血管化和骨形成进行组织学评估。与对照组相比，BMP-2显著增强了生物反应器内类骨质的形成。为了测试体内骨生物反应器作为肿瘤：骨相互作用的模型，FVB小鼠植入对照或BMP-2处理的生物反应器。6周后，将来源于乳腺肿瘤发生的多瘤病毒中间T（PyMT）模型的用荧光素酶标记的溶骨性诱导乳腺肿瘤细胞系（PyMT-Luc）经由股动脉递送至生物反应器。荧光素酶表达随时间的分析表明，与对照组相比，BMP-2处理的生物反应器中类骨质的存在显著提高了PyMT-Luc细胞的生长速率。这些数据提出了一个独特的异位骨形成的体内模型，可以操纵来解决与骨环境中的骨发育和肿瘤进展有关的分子问题。
A limited number of in vivo models that rapidly assess bone development or allow for the study of tumor progression in a closed in vivo environment exist. To address this, we have used bone tissue engineering techniques to generate a murine in vivo bone bioreactor. The bioreactor was created by implanting an osteoconductive hydroxyapatite scaffold pre-loaded with saline as a control or with bone morphogenetic protein-2 (BMP-2) to the murine femoral artery. Control and BMP-2 bioreactors were harvested and histologically assessed for vascularization and bone formation at 6 and 12 weeks post implantation. BMP-2 significantly enhanced the formation of osteoid within the bioreactor in comparison to the controls. To test the in vivo bone bioreactor as a model of tumor: bone interaction, FVB mice were implanted with control or BMP-2 treated bioreactors. After 6 weeks, an osteolytic inducing mammary tumor cell line tagged with luciferase (PyMT-Luc) derived from the polyoma virus middle T (PyMT) model of mammary tumorigenesis was delivered to the bioreactor via the femoral artery. Analysis of luciferase expression over time demonstrated that the presence of osteoid in the BMP-2 treated bioreactors significantly enhanced the growth rate of the PyMT-Luc cells in comparison to the control group. These data present a unique in vivo model of ectopic bone formation that can be manipulated to address molecular questions that pertain to bone development and tumor progression in a bone environment.