Autologous Stem Cell-Augmented Mandibular Distraction Osteogenesis

自体干细胞增强下颌牵引成骨

基本信息

批准号：
8855030
负责人：
Zongyang Sun
金额：
$ 34.65万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2016-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8855030
关键词：
Absorbable Gelatin Sponge Animal Model Animals Aspirate substance Autologous Autologous Transplantation Biomechanics Blood Platelets Bone Marrow Bone Marrow Transplantation Bone Regeneration Bone Transplantation Cell Proliferation Cell Survival Cell Transplantation Cells Coculture Techniques Congenital Abnormality Control Animal Data Defect Deformity Distraction Osteogenesis Effectiveness Exclusion Family suidae Fibrinogen Fracture Gel Germ Cells Goals Harvest Health Human In Vitro Infection Injection of therapeutic agent Injury Intervention Jaw Lead Lesion Life Mandibular distraction Marrow Mechanical Stimulation Mechanics Mesenchymal Stem Cell Transplantation Mesenchymal Stem Cells Methods Mission Modality Modeling Molecular Natural regeneration Operative Surgical Procedures Osteogenesis Osteotomy Patients Phase Plasma Population Protocols documentation Regenerative Medicine Risk Scheme Site Speed Stem cells Stretching Testing Thrombin Time Tissue Engineering Transplantation Treatment Failure Undifferentiated X-Ray Computed Tomography angiogenesis base bone bone cell clinical application clinically relevant craniofacial distraction expectation improved in vivo non-compliance osteogenic repaired scaffold skeletal standard care tibia tumor

项目摘要

DESCRIPTION (provided by applicant): Large craniofacial skeletal defects or deficiencies significantly compromise patient's life and remain challenging to treat. Distraction osteogenesis (DO), a mechanically-induced endogenous bone-regeneration approach, has been used as a major treatment modality. Though reliable in bone regeneration, the current DO approach is inefficient because it relies mostly on mechanical stimulation, hence requiring a substantially prolonged treatment time with heightened risks of infection, appliance breakage, noncompliance, and treatment failures. Consistent with the current NIDCR's mission on tissue engineering and regenerative medicine, this project has an overall goal to augment jaw bone regeneration by using mechanical stimulation combined with autologous stem cell-based tissue engineering approaches. The hypothesis is that mandibular DO can be significantly accelerated by the introduction of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) through scaffolds before distraction and booster BM-MSC injections during the consolidation phase. Young pigs, closely relevant to young humans who constitute the population commonly receiving craniofacial DO treatments, will be used. The project will first establish baseline parameters in control animals using our validated pig mandibular DO model. Aim 1 studies will then determine two critical aspects of introducing cells to the DO site, i.e., the use of undifferentiated or osteogenic-differentiated BM-MSCs, and the inclusion or exclusion of bone marrow-derived endothelial progenitor cells (BM-EPCs). Both of these aspects are highly relevant to osteogenesis and angiogenesis needed for bone regeneration, but no study to date has concurrently evaluated them in a DO site. Bone regeneration following cell transplantation will be compared to the baseline parameters derived from the controls in order to identify the lead osteogenic promoting combination. Next, the project will determine whether booster injection of BM-MSCs during the consolidation phase further improves bone regeneration (Aim 2). Bone regeneration following initial cell transplantation together with booster injections will e compared to that only with initial cell transplantation. The effects of using autologous platelet-rich plasma (PRP) to carry BM-MSCs for injections will also be determined by comparing the DO sites with PRP included in the injections versus DO sites without PRP. The combined data from Aim 1 and 2 will be employed to create an optimal treatment scheme to be evaluated in an accelerated DO protocols with a faster distraction and a shorter consolidation (Aim 3). These studies will determine whether or not an optimized DO with autologous stem cell intervention can substantially shorten (by several weeks) the DO treatment time while achieving similar quality and quantity of bone regeneration, compared to regular DO without cell augmentation. Overall, this project has the potential to establish a new paradigm for the management of large craniofacial bone deficiencies or defects using distraction osteogenesis.

描述（由申请人提供）：大的颅面骨骼缺陷或缺陷会严重影响患者的生活，并且治疗起来仍然具有挑战性。牵引成骨（DO）是一种机械诱导的内源性骨再生方法，已被用作主要的治疗方式。虽然目前的 DO 方法在骨再生方面可靠，但效率低下，因为它主要依赖于机械刺激，因此需要大大延长治疗时间，并且感染、矫治器破损、不依从性和治疗失败的风险增加。与当前 NIDCR 在组织工程和再生医学方面的使命一致，该项目的总体目标是通过使用机械刺激与基于自体干细胞的组织工程方法相结合来增强颌骨再生。假设是，在巩固阶段进行牵引和加强注射 BM-MSC 之前，通过支架引入自体骨髓来源的间充质干细胞 (BM-MSC)，可以显着加速下颌 DO。将使用与年轻人密切相关的幼猪，年轻人通常接受颅面溶解氧治疗。该项目将首先使用我们经过验证的猪下颌 DO 模型在对照动物中建立基线参数。然后，目标 1 研究将确定将细胞引入 DO 部位的两个关键方面，即使用未分化或成骨分化的 BM-MSC，以及包含或排除骨髓源性内皮祖细胞 (BM-EPC)。这两个方面都与骨再生所需的成骨和血管生成高度相关，但迄今为止还没有研究在 DO 部位同时评估它们。将细胞移植后的骨再生与来自对照的基线参数进行比较，以确定主要的成骨促进组合。接下来，该项目将确定在巩固阶段加强注射 BM-MSC 是否会进一步改善骨再生（目标 2）。初始细胞移植和加强注射后的骨再生将与仅初始细胞移植的骨再生进行比较。使用自体富血小板血浆 (PRP) 携带 BM-MSC 进行注射的效果也将通过比较注射中包含 PRP 的 DO 位点与不含 PRP 的 DO 位点来确定。目标 1 和 2 的综合数据将用于创建最佳治疗方案，并在加速 DO 方案中进行评估，该方案具有更快的分散注意力和更短的巩固时间（目标 3）。这些研究将确定与没有细胞增强的常规 DO 相比，采用自体干细胞干预的优化 DO 是否可以大幅缩短（几周）DO 治疗时间，同时实现相似的骨再生质量和数量。总体而言，该项目有可能为使用牵引成骨治疗大面积颅面骨缺陷或缺陷建立新的范例。