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首页> 外文期刊>Journal of orthopaedic research >Autologous implantation of BMP2-expressing dermal fibroblasts to improve bone mineral density and architecture in rabbit long bones
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Autologous implantation of BMP2-expressing dermal fibroblasts to improve bone mineral density and architecture in rabbit long bones

机译：自体植入表达BMP2的真皮成纤维细胞可改善兔长骨的骨矿物质密度和结构

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摘要

Cell-mediated gene therapy may treat bone fragility disorders. Dermal fibroblasts (DFb) may be an alternative cell source to stem cells for orthopedic gene therapy because of their rapid cell yield and excellent plasticity with bone morphogenetic protein-2 (BMP2) gene transduction. Autologous DFb or BMP2-expressing autologous DFb were administered in twelve rabbits by two delivery routes; a transcortical intra-medullar infusion into tibiae and delayed intra-osseous injection into femoral drill defects. Both delivery methods of DFb-BMP2 resulted in a successful cell engraftment, increased bone volume, bone mineral density, improved trabecular bone microarchitecture, greater bone defect filling, external callus formation, and trabecular surface area, compared to non-transduced DFb or no cells. Cell engraftment within trabecular bone and bone marrow tissue was most efficiently achieved by intra-osseous injection of DFb-BMP2. Our results suggested that BMP2-expressing autologous DFb have enhanced efficiency of engraftment in target bones resulting in a measurable biologic response by the bone of improved bone mineral density and bone microarchitecture. These results support that autologous implantation of DFb-BMP2 warrants further study on animal models of bone fragility disorders, such as osteogenesis imperfecta and osteoporosis to potentially enhance bone quality, particularly along with other gene modification of these diseases. (c) 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1455-1465, 2015.
机译：细胞介导的基因疗法可以治疗骨骼脆弱性疾病。真皮成纤维细胞（DFb）可能是骨科基因疗法中干细胞的替代细胞来源，因为它们具有快速的细胞产量和与骨形态发生蛋白2（BMP2）基因转导的出色可塑性。以十二种兔通过两种递送途径施用自体DFb或表达BMP2的自体DFb。胫骨经皮层髓内注射和股骨钻缺损延迟骨内注射。与未转导的DFb或无细胞相比，两种DFb-BMP2的递送方法均能成功植入细胞，增加骨体积，骨矿物质密度，改善小梁骨微结构，增强骨缺损，形成外部骨and和小梁表面积。通过骨内注射DFb-BMP2可以最有效地实现小梁骨和骨髓组织内的细胞移植。我们的结果表明，表达BMP2的自体DFb能够提高目标骨的植入效率，从而通过改善骨矿物质密度和骨微结构的骨骼产生可测量的生物学反应。这些结果支持自体植入DFb-BMP2值得对骨脆性疾病（例如成骨不全症和骨质疏松症）的动物模型进行进一步研究，以潜在地提高骨骼质量，尤其是与这些疾病的其他基因修饰一起。 （c）2015骨科研究学会。由Wiley Periodicals，Inc. J Orthop Res 33：1455-1465，2015年出版。

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