A NOVEL STEM CELL BASED DELIVERY SYSTEM TO IMPROVE BONE TISSUE REGENERATION

一种基于干细胞的新型输送系统，可改善骨组织再生

基本信息

批准号：
9318504
负责人：
Alireza Moshaverinia
金额：
$ 12.38万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
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：
2014-08-01 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9318504
关键词：
Address Adult Affect Alginates Anti-Inflammatory Agents Anti-inflammatory Apoptosis Aspirin Autologous Biocompatible Materials Bone Marrow Bone Regeneration Bone Tissue Bone Transplantation Calvaria Cell Communication Cell Survival Cells Cephalic Chemicals Coculture Techniques Collagen Coupled Data Defect Dental Dentistry Disadvantaged Down-Regulation Encapsulated Foundations Gene Expression Profiling Genetic Goals Gold Histologic Hydrogels Immune Immune system Immunocompromised Host Immunofluorescence Immunologic Impairment In Vitro Indomethacin Inflammatory Infusion procedures Injectable Interferon Type II Interleukin-17 Literature Macrophage Colony-Stimulating Factor Mediating Mesenchymal Differentiation Mesenchymal Stem Cells Modality Modeling Molecular Mus NF-kappa B Natural regeneration Nature Nerve Regeneration Neural Crest Organ Transplantation Orthopedics Osteogenesis Outcome PTGS2 gene Pathway interactions Patient-Focused Outcomes Porifera Procedures Process Property Reaction Regenerative Medicine Regulatory T-Lymphocyte Role Signal Transduction Skeletal bone Staining method Stains Stem cells System T-Lymphocyte TNF gene Testing Therapeutic Tissue Engineering Tissues Transplantation Up-Regulation Western Blotting Wild Type Mouse assault base bone cell type craniofacial cytokine deciduous tooth human stem cells improved in vivo innovation macrophage maxillofacial novel novel therapeutics orofacial osteogenic postnatal public health relevance reconstruction regenerative therapy repaired scaffold self-renewal skeletal subcutaneous tissue regeneration

项目摘要

DESCRIPTION (provided by applicant): Regeneration of craniofacial and skeletal bone defects has widely been achieved with bone grafting procedures. The literature suggests that there are more than one million cases of skeletal defects per year that require bone-graft procedures. Autologous bone has been considered the gold standard for such procedures. However, there are several disadvantages associated with this modality of treatment. The ability of stem cells to give rise to multiple specialized cell types along with their extensive distributin in many adult tissues make them an attractive target for application in bone tissue engineering. Dental MSCs such as stem cells from human exfoliated deciduous teeth (SHED) are attractive postnatal stem cells because they possess self-renewal and multilineage differentiation capacity as well as superior osteogenic properties compared to bone marrow mesenchymal stem cells (BMMSCs). The central hypothesis of this proposal is that an RGD-coupled alginate hydrogel scaffold can protect the encapsulated dental MSCs (SHED) from immune cells and cytokines in the early stages of transplantation, providing an appropriate physiochemical microenvironment for enhanced MSC viability and osteo-differentiation. It is hypothesized that these interactions are crucial in the osteogenic lineage commitment of dental MSCs. This proposal addresses a very important unresolved question: what is the role of the microenvironment (biomaterial) in dental MSC-immune cell interplay, fate determination of MSCs and osteogenic differentiation of MSCs. The validity of the central hypothesis will be tested by 1) determining how RGD-coupled alginate hydrogel as an encapsulating scaffold can interfere with the interplay between immune cells and dental MSCs in bone regeneration; 2) investigating the detailed mechanism of immune cell-induced MSC apoptosis; 3) developing a 3D alginate-based delivery system with anti-inflammatory function in the presence of indomethacin and 4) evaluating the effects of this delivery system on the bone regeneration properties of encapsulated MSCs. Upon successful completion of the Specific Aims, this project will improve our understanding of dental MSC-host immune interactions and introduce a promising MSC-based treatment approach for maxillofacial and skeletal defects. The result will be a novel injectable and biodegradable scaffold, presenting an innovative treatment modality for bone regeneration with therapeutic properties to manage local inflammatory reactions.

描述（由申请人提供）：通过骨移植程序广泛实现颅面和骨骼骨缺损的再生。文献表明，每年有超过100万例骨骼缺陷需要骨移植手术。自体骨被认为是此类程序的黄金标准。但是，这种治疗方式有几种缺点。干细胞在许多成年组织中产生多种专用细胞类型的能力以及它们在许多成年组织中的广泛分布素的能力使它们成为应用骨组织工程中的吸引力。与骨髓间充质干细胞（BMMSCS）相比，牙齿的MSC（例如，来自人类去角质的乳牙的干细胞（SHED）是有吸引力的产后干细胞，因为它们具有自我更新和多素分化的分化能力以及优质的成骨特性（BMMSCS）。该提案的中心假设是，在移植的早期阶段，RGD耦合的藻酸盐水凝胶支架可以保护包裹的牙齿MSC（SHED）免受免疫细胞和细胞因子的影响，从而提供了适当的生理学微环境，从而提供了增强的MSC ACITISIBILIOS和OSTEBIS和OSTEE OSTEO-OFTEO分解。假设这些相互作用对于牙科MSC的成骨谱系承诺至关重要。该提案解决了一个非常重要的未解决问题：微环境（生物材料）在牙科MSC免疫细胞相互作用，MSC的命运确定和MSC的成骨分化中是什么作用。中央假设的有效性将通过1）确定RGD偶联的藻酸盐水凝胶作为封装支架如何干扰免疫细胞与骨骼再生中的牙齿MSC之间的相互作用； 2）研究免疫细胞诱导的MSC凋亡的详细机制； 3）在存在吲哚美辛和4）评估该输送系统对封装MSC的骨再生性能的影响的情况下，开发具有抗炎功能的3D基于藻酸盐的递送系统。成功完成具体目标后，该项目将提高我们对牙科MSC - 宿主免疫相互作用的理解，并引入一种有希望的基于MSC的颌面和骨骼缺陷的治疗方法。结果将是一种新颖的注射且可生物降解的支架，具有具有治疗特性的骨再生的创新治疗方式，可管理局部炎症反应。