Efficient and rapid osteoinduction in an immune-competent host
Efficient and rapid osteoinduction in an immune-competent host
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DOI：
10.1089/hum.2006.190
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发表时间：
2007-08-01
影响因子：
4.2
通讯作者：
Davis, Alan R.
中科院分区：
文献类型：
--
作者：
Fouletier-Dilling, Christine M.;Gannon, Francis H.;Davis, Alan R.
骨诱导系统诱导有针对性的快速骨形成具有临床前景，但临床应用技术的开发必须在动物模型中进行测试，这往往是一个困难的挑战。我们之前已经证明，通过Ad5F35BMP2转导的人类细胞的植入，可以表达高水平的骨形态发生蛋白-2 (BMP2)，从而在目标部位快速形成骨。在该模型中包含人类细胞使我们无法在具有免疫能力的动物模型中测试该系统，从而限制了关于该方法有效性的信息。在这里，我们首次证明了BMP2诱导的软骨内骨形成在免疫功能不全的小鼠中使用人类细胞的系统和在免疫功能正常的动物中使用基于小鼠细胞的BMP2基因治疗系统之间的相似性。在这两种情况下，输送细胞都在5天内被迅速清除，而且在这两种情况下，它们似乎都没有在组织中形成任何结构。软骨内骨的形成经历了一系列高度有序的阶段，在形态和时间上，这两种模式是无法区分的。甚至对异位骨的长期分析也显示出相似的骨体积和最终的重塑形成相似的结构。结果表明，BMP2快速诱导骨形成的能力超越了免疫状态或传递细胞性质的贡献。
Osteoinductive systems to induce targeted rapid bone formation hold clinical promise, but development of technologies for clinical use that must be tested in animal models is often a difficult challenge. We previously demonstrated that implantation of human cells transduced with Ad5F35BMP2 to express high levels of bone morphogenetic protein-2 ( BMP2) resulted in rapid bone formation at targeted sites. Inclusion of human cells in this model precluded us from testing this system in an immune-competent animal model, thus limiting information about the efficacy of this approach. Here, for the first time we demonstrate the similarity between BMP2-induced endochondral bone formation in a system using human cells in an immune-incompetent mouse and a murine cell-based BMP2 gene therapy system in immune-competent animals. In both cases the delivery cells are rapidly cleared, within 5 days, and in neither case do they appear to contribute to any of the structures forming in the tissues. Endochondral bone formation progressed through a highly ordered series of stages that were both morphologically and temporally indistinguishable between the two models. Even long-term analysis of the heterotopic bone demonstrated similar bone volumes and the eventual remodeling to form similar structures. The results suggest that the ability of BMP2 to rapidly induce bone formation overrides contributions from either immune status or the nature of delivery cells.