Muscle Cell-Enhanced Cartilage Tissue Engineering

描述(申请人提供)：在美国，关节炎是导致残疾的主要原因。尽管关节炎在我们日益老龄化的社会中很普遍，但有效的关节炎治疗选择仍然有限。关节炎是由关节软骨的破坏引起的，并伴随着炎症和疼痛。软骨组织工程为软骨再生和组织功能恢复提供了一种很有前途的解决方案。然而，宿主部位的促炎细胞因子的存在不可避免地会导致基质的降解，导致工程化软骨不稳定。因此，为了将这项技术应用于临床，迫切需要设计出稳定的软骨，以抵抗促炎细胞因子诱导的降解。我们的长期目标是获得软骨调控的关键知识，并提高软骨组织工程技术的临床应用。我们正在开发一种新的策略，将发育生物学的概念和方法与组织工程的概念和方法相结合。在胚胎发育过程中，肌肉是与软骨组织一起发育的组织之一。我们广泛的初步研究表明，肌肉细胞在调节软骨内稳态和炎症刺激方面发挥着作用。我们的中心假设是，肌肉细胞和最佳支架选择可以通过增强软骨基质的产生和对促炎细胞因子的抵抗来增强工程软骨的稳定性。我们计划使用种植在3D丝质支架中的原代人类关节软骨细胞和间充质干细胞来验证这一假设。我们计划：1)研究肌肉细胞在调节软骨基质产生中的作用；2)研究肌肉细胞在调节促炎细胞因子反应中的作用；3)研究支架材料对肌肉细胞调节软骨基质产生和促炎细胞因子反应的影响。我们的研究团队由发育生物学、组织工程、免疫学和骨科领域的专家组成。我们相信，我们的协同努力和跨学科的方法将使我们对软骨稳态的调节和对促炎刺激的反应有更深入的了解，为建立和治疗关节炎提供基础知识。因此，我们的研究渴望满足提高组织工程技术的迫切需要，并可能导致开发一种新的策略来工程稳定的软骨用于临床应用。

DESCRIPTION (provided by applicant): Arthritis is a leading cause of disability in the United States. Despite its prevalence in our ever-aging society, effective treatment options for arthritis are still limited. Arthritis is caused by the destruction of joint cartilage, which is accompanied by inflammation and pain. Cartilage tissue engineering offers a promising solution to regenerate cartilage and restore tissue function. However, the presence of pro-inflammatory cytokines at the host site inevitably leads to matrix degradation, causing the engineered cartilage to be unstable. Therefore, for this technology to be applied clinically there is a critical need to engineer stable cartilage that is resistant to pro-inflammatory cytokine-induced degradation. Our long-term goal is to gain critical knowledge of cartilage regulation and enhance the technology of cartilage tissue engineering for clinical applications. We are developing a novel strategy that integrates concepts and approaches from developmental biology with those of tissue engineering. During embryogenesis, muscle is one of the tissues that develop alongside the presumptive cartilage tissue. Our extensive preliminary studies indicate a role of muscle cells in regulating cartilage homeostasis and inflammatory stimuli. Our central hypothesis is that muscle cells and optimal scaffold selection can be used to enhance the stability of engineered cartilage by enhancing cartilage matrix production and the resistance to pro-inflammatory cytokines. We plan to test this hypothesis by using primary human articular chondrocytes and mesenchymal stem cells seeded in 3D silk scaffolds. We plan to: 1) investigate the role of muscle cells in regulating cartilage matrix production, 2) investigate the role of muscle cells in regulating the response to pro-inflammatory cytokines, and 3) investigate the effect of scaffold material on muscle cell regulation of cartilage matrix production and the response to pro-inflammatory cytokines. Our research team consists of experts in the fields of developmental biology, tissue engineering, immunology and orthopaedics. We believe that our synergistic efforts and interdisciplinary approach will result in deeper understanding of the regulation of cartilage homeostasis and the response to pro- inflammatory stimuli, providing the fundamental knowledge for modeling and treating arthritis. Thus, our study aspires to meet the critical need of improving tissue engineering technology, and may lead to the development of a novel strategy to engineer stable cartilage for clinical applications.