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: 10194464
• 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/10194464
• 关键词: 3-Dimensional; Affect; Alginates; Anti-Inflammatory Agents; Attention; Biocompatible Materials; Bone Regeneration; Bone Tissue; Bone Transplantation; CD4 Positive T Lymphocytes; Cell Communication; 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 marrow mesenchymal stem cell; 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 cell survival; stem cell therapy; 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.

项目概要/摘要 颅面骨组织工程已通过骨移植手术广泛完成。 间充质干细胞（MSC）是有前途的骨再生替代治疗方式。间充质干细胞 源自口面部组织（例如牙龈间充质干细胞（GMSC））是有吸引力的产后干细胞 与具有自我更新和多谱系分化能力以及优越成骨特性的细胞相比 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。然而，控制移植干细胞的命运仍然是一个重大挑战。 了解影响封装间充质干细胞命运的因素具有重要的治疗意义。 水凝胶生物材料的弹性等物理力学特性已被证明是一个重要因素 影响 MSC 分化，但它们对 MSC 宿主免疫系统的作用尚不清楚。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封装如何 水凝胶生物材料弹性影响间充质干细胞-宿主免疫系统相互作用和免疫调节特性 间充质干细胞。因此，本提案的主要目标是（1）探讨海藻酸盐弹性的作用 水凝胶作为一种封装支架，在 MSCs-T 细胞中相互作用以及其背后的详细机制 间充质干细胞免疫调节。 (2) 研究封装生物材料的弹性对 MSC- T 细胞在 MSC 介导的骨组织工程中的相互作用。该提案的中心假设是 海藻酸盐水凝胶的弹性调节 MSCs-宿主免疫细胞（T 细胞）/细胞因子的相互作用，因此， 直接决定封装的 MSC 的命运。此外，假设水凝胶的弹性可以控制 因此，封装的 MSC 的免疫调节功能进一步调节微环境。之上 成功完成具体目标后，该项目将提高我们对 生物材料的物理力学特性对 MSC 存活和命运的决定。而且，它显着地 提高了我们对基质弹性如何调节 MSC 免疫调节特性的了解。

项目成果

Engineered Delivery of Dental Stem-Cell-Derived Extracellular Vesicles for Periodontal Tissue Regeneration.

用于牙周组织再生的牙科干细胞衍生的细胞外囊泡的工程化递送。

• 发表时间: 2022-06
• 影响因子: 10
• 作者: Zarubova, Jana;Hasani;Dashtimoghadam, Erfan;Zhang, Xuexiang;Ansari, Sahar;Li, Song;Moshaverinia, Alireza
• 通讯作者: Moshaverinia, Alireza

Antibacterial and Osteoinductive Implant Surface Using Layer-by-Layer Assembly.

采用逐层组装的抗菌和骨诱导植入物表面。

• 发表时间: 2021-09
• 影响因子: 7.6
• 作者: Hasani;Pouraghaei, S;Zahedi, E;Sarrion, P;Ishijima, M;Dashtimoghadam, E;Jahedmanesh, N;Ansari, S;Ogawa, T;Moshaverinia, A
• 通讯作者: Moshaverinia, A

Harnessing Dental Stem Cell Immunoregulation Using Cell-Laden Biomaterials.

使用充满细胞的生物材料利用牙科干细胞免疫调节。

• 发表时间: 2021
• 影响因子: 7.6
• 作者: Pouraghaei Sevari, S;Ansari, S;Chen, C;Moshaverinia, A
• 通讯作者: Moshaverinia, A