Bone morphogenetic protein-transduced human fibroblasts convert to osteoblasts and form bone in vivo
Bone morphogenetic protein-transduced human fibroblasts convert to osteoblasts and form bone in vivo
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DOI：
10.1089/107632702760184709
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发表时间：
2002-06-01
影响因子：
--
通讯作者：
Krebsbach, PH
中科院分区：
文献类型：
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作者：
Rutherford, RB;Moalli, M;Krebsbach, PH
用于局部骨形成的实验性细胞或离体基因疗法通常使用从骨膜或骨髓繁殖的骨祖细胞。这两种方法都需要进行骨或骨髓活检来获得细胞。我们已经证明，植入牙龈或皮肤成纤维细胞转导BMP离体，使用重组腺病毒（AdCMVBMP）连接到多孔生物可降解支架，在体内形成骨。在这里，我们表明，BMP-7转导成纤维细胞悬浮在注射热固性水凝胶形成完整的听小骨皮下注射和修复节段性缺损大鼠股骨。骨形成之前的中间软骨阶段。为了确定植入的转导细胞的命运，将离体BMP-7转导的或未转导的成纤维细胞的热固性水凝胶悬浮液置于扩散室中并植入以允许体内发育而不与宿主细胞直接接触。只有BMP转导的成纤维细胞在体内扩散室内形成骨，这表明BMP转导诱导这些细胞的成骨细胞转化。
Experimental cell or ex vivo gene therapy for localized bone formation typically uses osteoprogenitor cells propagated from periosteum or bone marrow. Both require bone or marrow biopsies to obtain cells. We have demonstrated that implantation of gingival or dermal fibroblasts transduced with BMP ex vivo, using a recombinant adenovirus (AdCMVBMP) attached to porous biodegradable scaffolds, form bone in vivo. Here we show that BMP-7-transduced fibroblasts suspended in injectable thermoset hydrogels form complete ossicles on subcutaneous injection and repair segmental defects in rat femurs. Bone formation was preceded by an intermediate cartilage stage. To determine the fate of the implanted transduced cells, thermoset hydrogel suspensions of ex vivo BMP-7-transduced or nontransduced fibroblasts were placed in diffusion chambers and implanted to allow development in vivo without direct contact with host cells. Only the BMP-transduced fibroblasts formed bone within the diffusion chambers in vivo, revealing that BMP transduction induces osteoblastic conversion of these cells.