Facilitating cartilage regeneration by heterogeneous progenitor cells

通过异质祖细胞促进软骨再生

• 批准号: 8333207
• 负责人: Ryan Michael Porter
• 金额: $ 24.7万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8333207
• 关键词: Affect; Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Arthritis; Articular Range of Motion; Biological; Caring; Cartilage; Cartilage injury; Cells; Chondrogenesis; Clinical; Complex; Defect; Degenerative polyarthritis; Deposition; Development; Environment; Goals; Healed; Human; Immunocompromised Host; In Situ; Incidence; Inflammation; Inflammatory; Instruction; Interleukin-1; Joints; Lead; Mediating; Mentors; Mesenchymal Stem Cells; Modeling; Monitor; Musculoskeletal; Natural regeneration; Operative Surgical Procedures; Oryctolagus cuniculus; Outcome; Pain; Pathogenesis; Phase; Play; Population; Process; Proliferating; Quality of life; Rattus; Regenerative Medicine; Reporter; Role; Secondary to; Shapes; Signal Transduction; Site; Stem cells; Surgical Injuries; TNF gene; Time; Tissue Engineering; Training Support; Transplantation; Trauma; Tumor Necrosis Factor-alpha; Work; articular cartilage; base; cartilage regeneration; cartilage repair; clinical application; cytokine; healing; improved; in vivo; injured; injury and repair; interest; joint injury; osteochondral tissue; post-doctoral training; regenerative; repaired; success; tissue regeneration; tool

Current standards of care for cartilage injuries cannot reliably provide sustained clinical improvement, so there is much interest in the development of alternative, biological approaches towards repair/regeneration. Regenerative medicine approaches typically involve the recruitment or transplantation of endogenous mesenchymal progenitor cells (MFCs) to the defect site. Under controlled conditions, these cells have the potential to proliferate, differentiate along the relevant musculoskeletal lineage and regenerate damaged tissue matrix. However, the intra-articular environment can be hostile to chondrogenesis; specifically, inflammation within the injured joint can inhibit tissue regeneration. Joint inflammation is mediated locally by cytokines such as interleukin-1 and tumor necrosis factor-a. Although proinflammatory cytokines play an important role in the pathogenesis of osteoarthritis, little is known about how they affect cartilage repair strategies involving MFCs. The central hypothesis shaping this project is that inflammation secondary to joint trauma or subsequent surgical intervention can inhibit the regenerative activity of MFCs within the cartilage defect, thus limiting repair. During the mentored phase, a toolset of reporter constructs were developed for monitoring the state of human MFC differentiation, using these constructs to non-invasively track inflammatory and chondrogenic activity within an immunocompromised rat model of cartilage injury. Upon transition to the independent phase of the project, tools developed during the mentored phase will help characterize the proinflammatory environment resulting from surgically-induced joint trauma, identifying factors that impair chondrogenesis and defect repair. Both immunologically-competent and -incompetent animal models of joint injury will be used to determine the ability of MFCs to repair/regenerate cartilage when protected from the identified factors. At the end of this project period, we will have a better understanding of how the joint environment - particularly inflammatory signaling - impacts the ultimate success of cartilage regeneration strategies using heterogeneous progenitor cell populations.

目前的软骨损伤护理标准不能可靠地提供持续的临床改善