Human Bone Morphogenetic Protein 2-Transduced Mesenchymal Stem Cells Improve Bone Regeneration in a Model of Mandible Distraction Surgery
Human Bone Morphogenetic Protein 2-Transduced Mesenchymal Stem Cells Improve Bone Regeneration in a Model of Mandible Distraction Surgery
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DOI：
10.1097/scs.0b013e318240fe9b
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发表时间：
2012-03-01
影响因子：
0.9
通讯作者：
Rojas-Martinez, Augusto
中科院分区：
文献类型：
--
作者：
Castro-Govea, Yanko;Cervantes-Kardasch, Victor H.;Rojas-Martinez, Augusto
背景：骨形态发生蛋白（BMP）积极参与骨化，BMP-2参与整个过程。使用表达腺病毒的 BMP 进行骨再生的基因治疗在小型哺乳动物中已取得成功，但在大型哺乳动物中的效果并不令人满意。方法：我们制备了包含自体间充质干细胞 (MSC) 的 3 组件植入物 (3C 移植物)，用表达 BMP-2 的腺病毒载体离体转导并嵌入脱矿的人骨基质 (DBM) 中。载体转导培养物中的成骨细胞数量和细胞外基质矿化程度高于对照组（用成骨培养基刺激的非转导 MSC 用作阳性对照，非转导 MSC 用作阴性对照）。三组件移植物用于填充杂种狗骨牵引手术造成的截骨。对照组包括仅进行骨牵引的狗和接受非转导的 MSC 移植物的狗。分散注意力 10 周后进行的放射照相随访显示，与对照组相比，巩固期显着缩短。提交进行解剖和组织学分析的死后下颌骨显示，3C 移植狗的重塑和骨成熟得到改善。在任何治疗区域均未观察到炎症浸润，也未检测到肝毒性。结论：我们通过使用 BMP-2 修饰的 MSC 植入物证明了狗模型中骨生成的加速，以进行骨牵引。这些结果对未来下颌骨牵引的临床试验有帮助。
Background: Bone morphogenetic proteins (BMPs) are actively involved in ossification, and BMP-2 participates throughout the entire process. Gene therapy for bone regeneration using adenovirus-expressing BMPs has been successful in small mammals, but it has not been satisfactory in large mammals.Methods: We generated a 3-component implant (3C graft) comprising autologous mesenchymal stem cells (MSCs), ex vivo transduced with an adenovirus vectorYexpressing BMP-2 and embedded in a demineralized human bone matrix (DBM).Results: In vitro studies demonstrated vector-induced osteogenesis; osteoblast population and mineralization of the extracellular matrix were greater in the vector-transduced cultures than in the controls (nontransduced MSCs stimulated with osteogenic media were used as positive controls, and nontransduced MSCs served as a negative control). The 3-component grafts were used to fill osteotomies created by bone distraction surgery in mongrel dogs. Control groups comprised dogs with bone distraction alone and dogs with nontransduced MSC grafts. The radiography follow-up, performed 10 weeks after distraction, demonstrated a remarkable reduction in the consolidation period compared with controls. Postmortem mandibles submitted for anatomic and histologic analyses showed improved remodeling and bone maturation in the 3C-grafted dogs. Inflammatory infiltrates were not observed in any of the treated areas, and no liver toxicity was detected.Conclusions: We demonstrated acceleration of osteogenesis in a dog model for bone distraction by using an implant of BMP-2 modified MSCs. These results are helpful for future clinical trials of mandible bone distraction.