Ex vivo-transduced autologous skin fibroblasts expressing human Lim mineralization protein-3 efficiently form new bone in animal models.
Ex vivo-transduced autologous skin fibroblasts expressing human Lim mineralization protein-3 efficiently form new bone in animal models.
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人LIM矿化蛋白（LMP）是一种新型的成骨细胞分化程序的细胞内正调控因子，其局部基因转移可以诱导啮齿动物有效的骨形成。为了开发一种临床相关的基因治疗方法，以促进骨愈合，我们使用了原代真皮成纤维细胞与Ad.LMP3体外转导，并接种在羟基磷灰石/胶原蛋白基质自体植入前。在这里，我们证明，基因修饰的自体皮肤成纤维细胞表达广告LMP-3能够诱导异位骨形成后植入的基质到小鼠三头肌和椎旁肌。此外，将Ad.LMP-3修饰的真皮成纤维细胞植入大鼠下颌骨临界尺寸缺损模型中导致有效愈合，如通过X射线、组织学和三维微计算机断层扫描（3DμCT）所确定的。这些结果证明了非分泌型细胞内成骨因子LMP-3在体内诱导骨形成中的有效性。此外，利用自体真皮成纤维细胞植入生物材料代表了一种有前途的方法，为未来可能的临床应用，旨在诱导新骨形成。
Local gene transfer of the human LIM Mineralization Protein (LMP), a novel intracellular positive regulator of the osteoblast differentiation program, can induce efficient bone formation in rodents. In order to develop a clinically relevant gene therapy approach to facilitate bone healing, we have used primary dermal fibroblasts transduced ex vivo with Ad.LMP3 and seeded on an hydroxyapatite/collagen matrix prior to autologous implantation. Here we demonstrate that genetically modified autologous dermal fibroblasts expressing Ad.LMP-3 are able to induce ectopic bone formation following implantation of the matrix into the mouse triceps and paravertebral muscles. Moreover, implantation of the Ad.LMP-3-modified dermal fibroblasts into a rat mandibular bone critical size defect model results in efficient healing as determined by X-ray, histology and three dimensional micro computed tomography (3DμCT). These results demonstrate the effectiveness of the non-secreted intracellular osteogenic factor LMP-3, in inducing bone formation in vivo. Moreover, the utilization of autologous dermal fibroblasts implanted on a biomaterial represents a promising approach for possible future clinical applications aimed at inducing new bone formation.
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DOI：
10.1007/s10856-006-0032-y
发表时间：
2008-01-01
影响因子：
3.7
作者：
Landi, Elena;Logroscino, Giandomenico;Sprio, Simone
通讯作者：
Sprio, Simone
影响因子：
64.5
作者：
Nakashima, K;Zhou, X;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
4.9
作者：
Tampieri, A;Celotti, G;Falini, G
通讯作者：
Falini, G
影响因子：
5.1
作者：
Pola, E;Gao, W;Robbins, P
通讯作者：
Robbins, P
影响因子：
5.1
作者：
Gugala, Z;Olmsted-Davis, EA;Davis, AR
通讯作者：
Davis, AR