Use of polymer-peptide system to deliver cells for intervertebral disc regeneration

利用高分子肽系统输送细胞进行椎间盘再生

• 批准号: 10255576
• 负责人: Francisco J SILVA
• 金额: $ 25.66万
• 依托单位: BIORESTORATIVE THERAPIES, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10255576
• 关键词: 3-Dimensional; Adolescent; Adult; Affect; American; Anabolism; Animal Experimentation; Animals; Anti-Inflammatory Agents; Autologous; Back; Behavioral; Biocompatible Materials; Biological Assay; Biology; Biomechanics; Bone Marrow; Caring; Cell Density; Cell Differentiation process; Cell Nucleus; Cell Survival; Cell Therapy; Cell Transplantation; Cell physiology; Cells; Chronic low back pain; Clinical Research; Coculture Techniques; Data; Deterioration; Dose; Encapsulated; Environment; Extracellular Matrix; Failure; Formulation; Functional disorder; Growth; Health; Height; Histologic; Homeostasis; Human; Human Engineering; Hydration status; Hydrogels; In Vitro; Inflammation; Inflammatory; Injectable; Injections; Intervertebral disc structure; Laminin; Legal patent; Low Back Pain; Magnetic Resonance Imaging; Methods; Modeling; Neck; Outcome; Outcome Measure; Pain; Pain management; Palliative Care; Pathologic; Peptides; Phase; Phenotype; Polymers; Production; Proteins; Proteolysis; Rattus; Recurrence; Reporter; Risk; Risk Factors; Roentgen Rays; Serum; Small Business Technology Transfer Research; Solid; Spinal Fusion; System; Technology; Therapeutic; Therapeutic Effect; Therapeutic Uses; Transplantation; Vertebral column; aged; base; biomaterial compatibility; cell type; chemokine; cost; crosslink; cytokine; design; disability; disc regeneration; effective therapy; immunoregulation; improved; in vivo; in vivo Model; interest; intervertebral disk degeneration; invention; mesenchymal stromal cell; microCT; novel; nucleus pulposus; pain relief; post-transplant; pre-clinical; reduce symptoms; response; socioeconomics; success; treatment effect

Abstract Low back pain affects millions of Americans and causes $100 billion socioeconomic loss annually. One of the prominent risk factors is intervertebral disc degeneration. Current treatments are palliative for relieving pain without restoring disc biology or biomechanics. Pain recurrence is common. Spinal fusion is popular, but it is limited by high failure rate (up to 30%) while predisposes adjacent discs to expedited deterioration. Immerging cell therapy is being actively developed with potential to halt or reverse disc degeneration while ameliorates symptoms. A recent invention of a peptide functionalized self-crosslinking polymer hydrogel has displayed initial evidence for improving the treatment effect of the therapeutic mesenchymal stromal cells on disc degeneration. To further investigate the therapeutic use of the new hydrogel material as a cell carrier, the present study is designed to investigate the working mechanism and optimize the formulation for treating disc degeneration and related low back pain. Accordingly there specific studies are designed targeting to investigate the impact of the hydrogel on the phenotype stability and cytokine release of the therapeutic donor cells, biosynthesis changes of host disc cells in response to the delivered donor cells, and therapeutic effect on the degenerated discs in the experimental animals using multiple in vitro and in vivo models. The present study will generate solid proof of concept data for the therapeutic use of the peptide-functionalized hydrogel in delivery of therapeutic cells for disc degeneration and related low back pain treatment.

抽象的 腰痛影响着数百万美国人，每年造成 1000 亿美元的社会经济损失。中的一个 突出的危险因素是椎间盘退变。目前的治疗方法只是缓解疼痛 无需恢复椎间盘生物学或生物力学。疼痛复发很常见。脊柱融合术很流行，但它 受到高故障率（高达 30%）的限制，同时会使相邻的椎间盘加速恶化。沉浸 细胞疗法正在积极开发中，有可能阻止或逆转椎间盘退变，同时改善 症状。最近发明的肽功能化自交联聚合物水凝胶显示 改善间充质基质细胞对椎间盘治疗效果的初步证据 退化。为了进一步研究新型水凝胶材料作为细胞载体的治疗用途， 本研究旨在研究其作用机制并优化治疗椎间盘的配方 退化和相关的腰痛。因此，有专门的研究旨在 研究水凝胶对治疗供体表型稳定性和细胞因子释放的影响 细胞、宿主椎间盘细胞响应所递送的供体细胞的生物合成变化以及对 使用多种体外和体内模型对实验动物中的退化椎间盘进行研究。目前的研究 将为肽功能化水凝胶的治疗用途生成可靠的概念数据证明 输送用于椎间盘退变和相关腰痛治疗的治疗细胞。