Bone Marrow Stromal Cells in Oral and Craniofacial Tissue Regeneration

描述（由申请人提供）：骨再生非常重要，特别是在口腔和颅面区域。创伤，包括口腔颌面部肿瘤的手术切除，会导致骨损伤和损伤。先天性疾病可能携带严重的组织缺陷，干扰正常功能，往往是毁容。这些疾病的最终治疗目标是使组织再生到正常或疾病前状态。我们的长期目标是确定参与牙齿和颅面组织再生的细胞和分子机制，并进一步开发骨骼再生和组织工程产品。本申请的目的是确定成体干细胞在组织再生中的来源和潜力，并阐明osterix（Osx）（一种关键的成骨转录因子）在骨和牙本质形成细胞分化中的作用。有待检验的中心假设是，骨髓来源的细胞能够再生口腔颅面组织，Osx刺激骨合成代谢行为的正常级联。其基本原理是基于以下证据：骨髓来源的未分化间充质干细胞转化为成熟和功能性成骨细胞和成牙本质细胞是骨和牙本质形成以及再生的关键步骤。目的1：探讨骨髓基质细胞（BMSCs）在口腔颌面部再生中的分化潜能及组织发生。使用基于细胞的方法，将基因标记的BMSC引入口腔，牙齿和颅面伤口，并首次记录活动物中的细胞分化，迁移以及随后的骨和牙本质形成。目的2：探讨Osx在骨再生和组织工程中促进骨髓基质细胞分化的作用及机制。使用基因治疗策略，Osx将特异性靶向骨髓和/或局部组织来源的细胞，并且第一次，Osx促进细胞分化和增强骨生成和牙本质生成的作用将在新的转基因模型中确定。这些活体动物研究的结果将有助于确定新的细胞来源，这是组织工程最重要的元素和最强大的引擎。这些研究也将为使用基因治疗方法的骨和牙齿组织形成提供新的和重要的见解，这肯定会使口腔和颅面区域有组织缺损，损伤和损伤的患者受益。

DESCRIPTION (provided by applicant): Bone regeneration is of enormous importance, particularly in the oral and craniofacial region. Trauma, including surgical removal of tumors in the oral and maxillofacial region, causes bone damage and injury. Congenital disorders may carry severe tissue defects that interfere with normal function and are often disfiguring. The ultimate therapeutic goal for these diseases is regeneration of the tissues to a normal or pre-disease state. Our long-range goal is to determine the cellular and molecular mechanisms involved in the regeneration of dental and craniofacial tissues and to further the development of products for skeletal regeneration and tissue engineering. The objectives of this application are to determine the source and potential of adult stem cells in tissue regeneration and to elucidate the roles of osterix (Osx), a critical osteogenic transcription factor, in the differentiation of bone- and dentin-forming cells. The central hypotheses to be tested are that marrow-derived cells are capable of regenerating oral craniofacial tissues and Osx stimulates the normal cascade of bone anabolic behavior. The rationale is based on the evidence that the conversion of marrow-derived non-differentiated mesenchymal stem cells into mature and functional osteo- and odonto-blasts is a crucial step in bone and dentin formation, as well as in regeneration. Aim 1: To determine the differentiation potential and histogenesis of bone marrow stromal cells (BMSCs) in oral craniofacial regeneration. Using a cell-based approach, the genetically labeled BMSCs will be introduced into oral, dental and craniofacial wounds and, for the first time, the cell differentiation, migration, and subsequent bone and dentin formation in a live animal will be documented. Aim 2: To determine, in vivo, the effects and mechanisms of Osx in promoting BMSC differentiation in bone regeneration and tissue engineering. Using a gene-therapy strategy, Osx will specifically target the bone- marrow and/or local-tissue derived cells, and for the first time, the effects of Osx promoting cell differentiation and enhancing osteogenesis and dentinogenesis will be determined in a novel transgenic model. Results derived from these studies in live animals will help identify new sources of cells, which are the most important element and most powerful engine for tissue engineering. These investigations will also provide novel and important insights into bone and tooth tissue formation using a gene-therapy approach, which will certainly benefit the patients who have tissue defects, damages and injuries in mouth as well as craniofacial regions.