iPS cell generation from jaw periosteum: is the resulting osteogenic capacity more efficient?

口腔颌面外科领域迫切需要新的有效的治疗方法，以使特别是大型骨缺损得以再生。组织工程策略代表了最有前途的治疗方案。颌骨骨膜细胞在咀嚼过程中能承受高机械负荷的独特特性，使其成为口腔颌面外科细胞治疗的候选细胞。在我们联合项目的第一个资助期，我们首次从颌骨骨膜细胞中诱导出多能干细胞，并成功发表了这项工作。我们建立了一个完全无异种的方案，并使用了一种自我复制的RNA结构，以执行无足迹的细胞重新编程。下一步，我们从这些iPS细胞中培养出诱导的间充质基质细胞(IMSCs)，并在2D培养中显示出强大的矿化潜力。鉴于未来的临床应用，我们继续开发iMSC种植的三维结构，并利用免疫缺陷小鼠模型测试细胞功能(特别是分化潜能)和构建结构的体内生物相容性。通过本项目的实现，我们为骨组织工程开辟了新的干细胞来源，并为iPS细胞治疗建立了一条临床适用的途径。

New and effective therapies are urgently needed in the field of oral and maxillofacial surgery to enable regeneration of in particular large bone defects. Tissue engineering strategies represent the most promising therapeutic option.The unique specialization of jaw periosteal cells (JPCs) withstanding high mechanical load during mastication, makes them to attractive candidates for cell-based therapies for oral and maxillofacial surgeries.In the first funding period of our joint project, we generated for the first time induced pluripotent stem (iPS) cells from jaw periosteal cells and successfully published this work. We established a completely xeno-free protocol and used a self-replicating RNA construct in order to perform a footprint-free cell reprogramming. In the next step, we generated induced mesenchymal stromal cells (iMSCs) from these iPS cells, which in turn showed strong mineralization potential in 2D culture.In view of future clinical application, we move forward to develop iMSC-seeded 3D constructs and test cell functions (particularly the differentiation potential) and biocompatibility of constructs in vitro and in vivo by using an immunodeficient mouse model.By the realization of this project, we open up a new stem cell source for bone tissue engineering and establish a clinically applicable approach for iPS cell-based therapies.