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

• 批准号: 9145384
• 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
• 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/9145384
• 关键词: Adult; Affect; Alginates; Anti-Inflammatory Agents; Anti-inflammatory; Apoptotic; Aspirin; Autologous; Autophagocytosis; Biocompatible Materials; Bone Marrow; Bone Regeneration; Bone Tissue; Bone Transplantation; Bone necrosis; Calvaria; Cell Survival; Cells; Cessation of life; Characteristics; Coculture Techniques; Collagen; Complex; Defect; Dental; Dentistry; Development; Disadvantaged; Drug Delivery Systems; Encapsulated; Engineering; Extracellular Matrix; Foundations; Goals; Gold; Health; Hydrogels; IL17 gene; Immune; Immune system; Immunocompromised Host; Immunofluorescence Immunologic; In Vitro; Indomethacin; Inflammatory; Infusion procedures; Injectable; Interferons; Jaw; Link; Literature; Macrophage Colony-Stimulating Factor; Mediating; Mesenchymal Stem Cells; Microencapsulations; Modality; Modeling; Mus; Natural regeneration; Nature; Neural Crest; Organ Transplantation; Orthopedics; Osteogenesis; Osteolysis; Outcome; Pathologic; Pathway interactions; Performance; Periodontitis; Pharmaceutical Preparations; Pharmacological Treatment; Phenotype; Porifera; Property; Reaction; Regenerative Medicine; Regulatory T-Lymphocyte; Reporting; Role; Site; Skeletal bone; Source; Staining method; Stains; System; T-Lymphocyte; TNF gene; Testing; Therapeutic; Tissue Engineering; Tissues; Transplantation; Wild Type Mouse; annexin A5; base; bone; cell type; craniofacial; cytokine; extracellular; immune function; improved; in vivo; innovation; macrophage; maxillofacial; novel; novel therapeutics; osteogenic; postnatal; protective effect; regenerative; repaired; scaffold; self-renewal; skeletal; stem cell fate; stem cells; subcutaneous; success; tissue regeneration

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 a year that require bone-graft procedures. Autologous bone has been considered the gold standard for bone augmentation. 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 have made them an attractive target for application in bone tissue engineering. Dental MSCs are attractive postnatal stem cells with self-renewal and multilineage differentiation capacity having superior osteogenic properties in comparison to bone marrow mesenchymal stem cells (BMMSCs). The central hypothesis of this proposal is that alginate-based drug delivery system regulates the cross-talk between immune cells and dental MSCs in bone regeneration. It is hypothesized that these interactions are crucial in the osteogenic lineage commitment of dental MSCs. This proposal tries to find answers for a very important and unanswered question: what is the role of the microenvironment (biomaterial) in the interplay between MSCs and immune cells in the fate determining and osteogenic differentiation of MSCs. The validity of the central hypothesis will be tested by determining: 1) the role of biomaterial in the interplay between immune cells and dental MSCs in MSC-mediated bone regeneration, using different inflammatory cytokines (e.g. IL17, IFN-�, TNF-�, and M-CSF), and different immune cell (e.g. Th1, Th17, Treg, and macrophage) via in vitro and in vivo studies; 2) the immune-protective effects of biomaterial on survival and viability of dental MSCs using immunofluorescence staining (Annexin V for apoptotic pathway and LC3 for autophagy); 3) the possibility of development and characterization of a novel MSC microencapsulation system based on alginate containing anti- inflammatory drug (indomethacin) for improved bone regeneration. 3D injectable model with the ability of site- specific pharmacological treatment will be developed to test the role of biomaterial in the interplay between immune cells and MSC in bone regeneration. This proposal will provide a novel injectable and biodegradable scaffold for encapsulation of dental MSC, presenting an innovative treatment modality for bone regeneration with therapeutic properties to manage local inflammatory reactions.

描述（通过应用提供）：通过骨移植程序广泛实现了颅面和骨骼骨缺损的再生。文献表明，每年有超过一百万例骨骼缺陷需要骨移植手术。自体骨被认为是骨骼增强的黄金标准。但是，有几种与这种治疗方式有关的灾难。干细胞在许多成人时机中产生多种专用细胞类型的能力以及它们广泛的分布蛋白使它们成为在骨组织工程中应用的有吸引力的目标。与骨髓间充质干细胞相比，牙科MSC是具有自我更新和多曲线分化能力具有优质成骨特性的吸引人的产后干细胞（BMMSCS）。该提议的中心假设是，基于藻酸盐的药物递送系统调节骨再生中免疫细胞和牙齿MSC之间的串扰。假设这些相互作用对于牙科MSC的成骨谱系承诺至关重要。该提议试图找到一个非常重要且未解决的问题的答案：微环境（生物材料）在MSC和免疫细胞之间在MSC的脂肪确定和成骨分化中的相互作用中的作用是什么。中央假设的有效性将通过确定：1）使用不同的炎症细胞因子（例如IL17，IFN- ifn-，tnf-- and tnf- and tnf- and tnf）和不同的Immunocells（threg and threg and threg and threg and threg and threg and threg and threg and threg and threg and threg and threg and threg and th1，th17 threg and th117通过体外和体内研究； 2）生物材料对使用免疫荧光染色的牙科MSC生存和生存能力的免疫保护作用（用于凋亡途径的膜联蛋白V和自噬的LC3）； 3）基于含有抗炎药（吲哚美辛）的藻酸盐的新型MSC微囊化系统的开发和表征的可能性，以改善骨骼再生。具有特异性药物处理能力的3D注射模型将 可以开发生物材料在免疫细胞与MSC之间的相互作用中的作用。该提案将提供一种新颖的注射且可生物降解的支架，用于封装牙科MSC，并具有具有治疗特性的骨骼再生的创新治疗方式，以管理局部炎症反应。