Anabolic Interventions in Engineered Cartilage and Degenerative Joint Disease

工程软骨和退行性关节疾病的合成代谢干预

• 批准号: 7964090
• 负责人: Richard Spencer
• 金额: $ 29.71万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7964090
• 关键词: Aging; Animal Model; Animals; Attenuated; Benchmarking; Biochemical; Birds; Cartilage; Cattle; Cells; Chondrocytes; Degenerative polyarthritis; Disease; Engineering; Goals; Growth; Growth Factor; Growth and Development function; Human; In Vitro; Intervention; Magnetic Resonance Imaging; Maintenance; Mechanical Stimulation; Messenger RNA; Molecular; Phenotype; Physiologic pulse; Process; Production; Source; Tissues; Translating; Ultrasonography; Work; articular cartilage; human subject; in vivo; prevent; repaired

We are establishing defined molecular, biochemical, and non-invasive magnetic resonance (MR) imaging benchmarks for articular cartilage from animals and humans. Our aim is to demonstrate that engineered cartilage will support viability of and matrix production from mammalian chondrocytes using a young bovine source, establish tissue growth which will be qualitatively similar to that produced from avian cells under comparable conditions, and establish maintenance of the hyaline phenotype. We wish to apply mechanical stimulation of chondrocytes and cartilage by application of pulsed low-intensity ultrasound (PLIUS) so as to increase expression of matrix-related mRNA and corresponding matrix production, the goal being to upregulate repair processes in an animal model of osteoarthritis (OA). Ultimately we wish to establish whether these in vitro and animal model effects will translate into treatment of OA in aging humans; that is, investigate the potential of PLIUS as a disease-modifying intervention in human subjects with early OA. Additional work involves administration of exogenous growth factors to developing tissue, both by itself and in combination with PLIUS.

我们正在建立定义的分子，生化和非侵入性磁共振（MR）成像基准，用于来自动物和人类的关节软骨。 我们的目的是证明，工程的软骨将支持使用年轻的牛来源从哺乳动物软骨细胞中生产和基质产生的生存能力，并建立组织生长，这将在质量上与在可比条件下从鸟类细胞产生的质量相似，并确定透明透明表型的维持。 我们希望通过应用脉冲低强度超声（PLIUS）应用机械刺激软骨细胞和软骨，以增加基质相关的mRNA的表达和相应的基质产生，其目的是上调骨关节炎动物模型（OA）中的动物模型中的修复过程。 最终，我们希望确定这些体外和动物模型的影响是否会转化为衰老人类的OA的治疗。也就是说，研究Plius作为对早期OA的人类受试者的疾病改良干预的潜力。 额外的工作涉及给予外源生长因子以本身和与Plius结合进行组织。