The role of elasticity of biomaterials on the stem cell-host immune cell interplay

生物材料的弹性对干细胞-宿主免疫细胞相互作用的作用

• 批准号: 10041630
• 负责人: Alireza Moshaverinia
• 金额: $ 15.6万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10041630
• 关键词: 3-Dimensional; Affect; Alginates; Anti-Inflammatory Agents; Attention; Biocompatible Materials; Bone Marrow; Bone Regeneration; Bone Tissue; Bone Transplantation; CD4 Positive T Lymphocytes; Cell Communication; Cell Survival; Cell Therapy; Cells; Chemicals; Coculture Techniques; Dental; Elasticity; Encapsulated; GTP-Binding Protein alpha Subunits, Gs; Genetic; Gingiva; Goals; Histologic; Hydrogels; Immune; Immune system; Immunocompromised Host; Immunofluorescence Immunologic; Implant; In Vitro; Incubated; Indomethacin; Infiltration; Inflammatory; Infusion procedures; Interferon Type II; Interleukin-17; Knowledge; MAP Kinase Gene; Mediating; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Modality; Mus; NF-kappa B; Natural regeneration; Nature; Oral cavity; Organ Transplantation; Orthopedics; Osteogenesis; Pathway interactions; Patient-Focused Outcomes; Property; Regulation; Regulatory T-Lymphocyte; Reporting; Role; Site; Stem cell transplant; System; T-Lymphocyte; TNF gene; Testing; Therapeutic; Tissue Engineering; Tissue Sample; Tissues; Transplantation; Western Blotting; alternative treatment; base; bone; bone quality; clinical application; craniofacial bone; cytokine; immunoregulation; improved; in vivo; interest; orofacial; osteogenic; postnatal; public health relevance; regenerative; regenerative therapy; scaffold; self-renewal; stem cell differentiation; stem cell fate; stem cells; subcutaneous; tissue regeneration

Project Summary/Abstract Craniofacial bone tissue engineering has been extensively accomplished using bone grafting procedures. Mesenchymal stem cells (MSCs) are promising alternative treatment modality for bone regeneration. MSCs derived from orofacial tissues (e.g. gingival mesenchymal stem cells (GMSCs)) are attractive postnatal stem cells with self-renewal and multilineage differentiation capacities and superior osteogenic properties compared to bone marrow mesenchymal stem cells (BMMSCs). It is well known that biomaterials can be used to direct the fate of stem cells. However, controlling the fate of the transplanted stem cells is still a major challenge. Understanding the factors influencing the fate of encapsulating MSCs is of major therapeutic interest. Physiomechanical properties such as elasticity of the hydrogel biomaterial have been shown to be a vital factor influencing MSC differentiation, but their role on the MSC-host immune system is fairly unknown. To develop effective MSC- based regenerative therapies it is crucial to have a clear understanding of how the encapsulating hydrogel biomaterial elasticity affect the MSCs-host immune system interplay and immunoregulatory properties of MSCs. Therefore, the main objectives of this proposal are to (1) to explore the role of the elasticity of alginate hydrogel, as an encapsulating scaffold, in MSCs-T cells interplay and the detailed mechanism underlying the MSC immunomodulation.; and (2) To Investigate the role of elasticity of the encapsulating biomaterial on MSC- T cell interplay in the MSC-mediated bone tissue engineering. The central hypothesis of this proposal is that the elasticity of alginate hydrogel regulates the MSCs-host immune cells (T-cells)/ cytokines interplay, therefore, direct the fate of the encapsulated MSCs. Also, it is hypothesized that hydrogel elasticity can control the immunoregulatory function of the encapsulated MSCs, therefore, further regulates the microenvironment. Upon successful completion of the Specific Aims, this project will improve our understanding of the critical role of the biomaterials physiomechanical properties on MSC survival and fate determination. Moreover, it significantly improves our knowledge on how the matrix elasticity modulates MSCs' immunomodulatory properties.

项目摘要/摘要 颅面骨组织工程已经使用骨移植程序广泛完成。 间充质干细胞（MSC）是骨再生的有前途的替代治疗方式。 MSC 源自口面组织（例如牙龈间充质干细胞（GMSC））是有吸引力的产后茎 比较具有自我更新和多节分分化能力和优质成骨特性的细胞 到骨髓间充质干细胞（BMMSC）。众所周知，生物材料可用于指导 干细胞的命运。但是，控制移植的干细胞的命运仍然是一个主要挑战。 了解影响封装MSC的命运的因素具有主要的治疗兴趣。 生理力学特性（例如水凝胶生物材料的弹性）已被证明是至关重要的因素 影响MSC差异化，但是它们在MSC-host免疫系统中的作用是相当未知的。发展 有效的基于MSC的再生疗法至关重要的是要清楚地了解如何封装 水凝胶生物材料弹性影响MSC-HOST免疫系统相互作用和免疫调节特性 MSC。因此，该提案的主要目标是（1）探索藻酸盐弹性的作用 水凝胶作为封装支架，在MSCS-T细胞相互作用和详细机制中 MSC免疫调节。 （2）研究封装生物材料对MSC-的弹性的作用 MSC介导的骨组织工程中的T细胞相互作用。该提议的核心假设是 藻酸盐水凝胶的弹性调节MSC宿主免疫细胞（T细胞）/细胞因子相互作用，因此 指导封装的MSC的命运。同样，假设水凝胶弹性可以控制 因此，封装的MSC的免疫调节功能进一步调节了微环境。之上 成功完成具体目标，该项目将提高我们对 生物材料对MSC生存和命运确定的生理力学特性。而且，它很大程度上 提高了我们对矩阵弹性如何调节MSC的免疫调节特性的知识。