TOWARDS ELECTRICALLY ENRICHED MESENCHYMAL STEM CELLS FOR TREATMENT OF EARLY INFLAMMATORY OSTEOARTHRITIS

项目摘要 骨关节炎(OA)是一种致残性、退行性疾病，累及关节的每一个组织。炎症性的 这些组织周围的环境被认为是OA发病的根本原因，并可能 因此掌握一把治疗的钥匙。这种失调的炎症状态的一个突出的最终结果是长期- 术语，进行性软骨组织退化。有效的疾病修正治疗可以干预这一点 降级级联目前不可用。人骨髓间充质干细胞(HMSC)注射 由于其多方面的免疫调节作用，有望成为治疗骨性关节炎的潜在疾病调整疗法 属性。然而，hMSC注射在疗效上存在很大的差异，这可以归因于 部分原因是使用包含显著种群异质性/细胞状态的细胞的固有复杂性 不同程度的衰老。因此，我们建议：1)开发一种基于hMSCs的治疗方法 电性能与优良的茎和免疫调节/再生能力有关，以及2) 用早期电浓缩hMSCs的体外模型评估其治疗潜力 炎症性骨关节炎。我们设想，电浓缩可以作为hMSC的一个新组件来实现 骨性关节炎的抗炎促再生疗法。

PROJECT ABSTRACT Osteoarthritis (OA) is a disabling, degenerative disease that involves every tissue in the joint. The inflammatory environment surrounding these tissues is believed to fundamentally underlie OA pathogenesis and may therefore hold a key to treatment. One prominent end result of this dysregulated inflammatory state is long- term, progressive cartilage tissue degradation. Effective disease modifying treatments that can intervene in this degradative cascade are not currently available. Human mesenchymal stem cell (hMSC) injections are emerging as a potential disease modifying treatment for OA due to their multi-faceted immunomodulatory properties. However, hMSC injections suffer from substantial variability in efficacy which can be attributed in part to the inherent complexity of using cells which contain significant population heterogeneity/cell states with varying levels of senescence. We therefore propose: 1) to develop a therapy based on hMSCs enriched for electrical properties associated with superior stemness and immunomodulatory/regenerative capacity and 2) to assess the therapeutic potential of these electrically enriched hMSCs using an in vitro model of early inflammatory OA. We envision that electrical enrichment can be implemented as a novel component of hMSC therapy for combating inflammation and promoting regeneration in OA.