Mesenchymal Stem Cells Derived from Human Gingiva (GMSC) Inhibit Bone Erosion in Autoimmune Arthritis

源自人牙龈的间充质干细胞 (GMSC) 可抑制自身免疫性关节炎中的骨侵蚀

• 批准号: 10089513
• 负责人: WAEL N JARJOUR
• 金额: $ 39万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10089513
• 关键词: Affect; American; Animal Model; Arthritis; Autoimmune Diseases; Autologous; Biological; Bone Density; Cartilage; Cells; Characteristics; Chronic; Collagen Arthritis; Disease; Evaluation; Fibroblasts; Gingiva; Health; Hip Fractures; Human; Immune response; Immunosuppression; In Vitro; Incidence; Inflammatory Arthritis; Lead; Learning; Magnetic Resonance Imaging; Marrow; Mediating; Mesenchymal Stem Cells; Modeling; Molecular; Morphology; Mus; Natural regeneration; Organ; Osteoclasts; Osteoporosis; Osteoporotic; Outcome; Pain; Patients; Phase; Phenotype; Prevention; RNA; Resistance; Rheumatoid Arthritis; Risk; Severities; Spinal Fractures; Stains; Structure; Synovitis; Testing; Therapeutic; Therapeutic Effect; Therapeutic Studies; Tissues; Toxic effect; Transcript; Validation; arthritis therapy; autoimmune arthritis; base; bone; bone erosion; chronic pain; disability; experience; experimental study; fracture risk; human model; humanized mouse; immunoregulation; improved; in vivo; innovation; joint destruction; joint injury; microCT; migration; mouse model; novel strategies; prevent; repaired; tartrate-resistant acid phosphatase

Abstract Current state-of-the-art treatment of rheumatoid arthritis (RA) is not curative and is associated with considerable toxicity. Bone erosion and cartilage damage are the most severe complications of RA and the major reasons for pain and disability in this disease. They are also key targets that are resistant to current therapies. Substantial evidence now exists that mesenchymal stem cells (MSC) have regeneration ability and immunomodulatory functions that could contribute to treatment of autoimmune diseases. Nonetheless, it is unknown whether MSC, particularly those derived from gingival tissues (GMSC) can directly affect bone and cartilage protection. Based on our preliminary observations, we make a bold hypothesis that GMSC can directly inhibit the formation of osteoclasts and activities of inflamed synovial tissues and through these mechanisms can prevent bone erosion and cartilage damage in rheumatoid arthritis. The study will include two phases (R61 and R33) with three specific aims. For the R61 phase, specific aim 1 and 2 will test the hypothesis that GMSC suppress osteoclast differentiation and activities, as well as activation and function of inflamed synovial tissues in the in vitro and in vivo with collagen-induced arthritis (CIA) model and in the R33 phase (Specific aim 3) a further validation will be conducted using a humanized model. When successfully completed, this project will help us understand the characteristics of GMSC in protecting bone erosion and cartilage damage in autoimmune arthritis and may lead to a potential therapeutic strategy for RA and other human autoimmune diseases.

摘要 目前最先进的类风湿性关节炎(RA)治疗方法并不能治愈，而且与 相当大的毒性。骨侵蚀和软骨损伤是类风湿关节炎最严重的并发症。 这种疾病中疼痛和残疾的主要原因。他们也是抵抗当前潮流的关键目标 治疗。大量证据表明，间充质干细胞(MSC)具有再生能力和 可能有助于自身免疫性疾病治疗的免疫调节功能。尽管如此，它仍然是 目前尚不清楚间充质干细胞，尤其是牙周组织来源的间充质干细胞是否能直接影响骨骼和牙周组织 保护软骨。基于我们的初步观察，我们做出了一个大胆的假设，即GMSC可以 直接抑制破骨细胞的形成和炎症滑膜组织的活性，并通过这些 机制可以预防类风湿性关节炎的骨侵蚀和软骨损伤。该研究将包括两项 阶段(R61和R33)，有三个具体目标。对于R61阶段，特定目标1和2将测试 假设GMSC抑制破骨细胞分化和活性，以及激活和功能 胶原性关节炎(CIA)模型和R33模型的体内外炎症滑膜组织 阶段(具体目标3)将使用人性化模型进行进一步验证。当成功时 项目完成后，将帮助我们了解GMSC在保护骨侵蚀和骨侵蚀方面的特点 自身免疫性关节炎中的软骨损伤，可能导致一种潜在的RA和 其他人类自身免疫性疾病。