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）：大型颅面骨骼缺陷或缺陷严重损害了患者的生活，并且仍然具有挑战性。分散骨化（DO）是一种机械诱导的内源性骨骼再生方法，已被用作主要的治疗方式。尽管骨骼再生可靠，但当前的DO方法效率低下，因为它主要依赖于机械刺激，因此需要大幅度延长治疗时间，并增加感染风险，设备损失，不合规和治疗失败。与当前NIDCR在组织工程和再生医学方面的任务一致，该项目的总体目标是通过使用机械刺激与自体干细胞基于基于干细胞的组织工程方法相结合来增强下颌骨再生。该假设是，通过在整合阶段，通过脚手架引入自体骨髓衍生的间充质干细胞（BM-MSC），可以通过引入自体骨髓衍生的间充质干细胞（BM-MSC）来显着加速下颌DO。将使用与构成通常接受颅面DO治疗的人群密切相关的年轻猪。该项目将首先使用我们经过验证的Pig下颌DO模型在对照动物中建立基线参数。 AIM 1研究将确定将细胞引入DO位点的两个关键方面，即使用未分化或成骨分辨率分化的BM-MSC，以及骨髓衍生的内皮祖细胞（BM-EPC）的包含或排除。这两个方面都与骨再生所需的成骨和血管生成高度相关，但是迄今为止，尚无研究在DO部位同时对其进行评估。细胞移植后的骨再生将与从对照中得出的基线参数进行比较，以鉴定铅成骨的促进组合。接下来，该项目将确定在巩固阶段的BM-MSC注射是否进一步改善骨骼再生（AIM 2）。与初始细胞移植相比，初始细胞移植后的骨再生以及助推器注射的骨骼将E。使用富含血小板的血浆（PRP）携带BM-MSC进行注射的影响也将通过比较注射中的PRP与没有PRP的位点的DO位点来确定。 AIM 1和2的组合数据将用于创建最佳的治疗方案，以在加速的DO协议中评估，并以更快的分心和较短的整合度进行评估（AIM 3）。这些研究将确定对自体干细胞干预的优化是否可以显着缩短（到几周），而DO治疗时间则在实现相似的质量和骨骼再生的同时，与常规DO相比，没有细胞增强。总体而言，该项目有可能建立一个新的范式，用于使用分散骨质发生的大型颅面骨缺陷或缺陷。