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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的腰痛会影响数百万美国人，并每年造成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变性。当前治疗对缓解疼痛的姑息治疗不恢复椎间盘生物学或生物力学。疼痛复发很常见。脊柱融合很受欢迎，但是受高功能率（最高30％）的限制，而易于加快椎间盘加速恶化。沉浸细胞疗法正在积极开发，并有可能停止或反向椎间盘变性，同时改善症状。最近显示的肽功能化自联合聚合物水凝胶的发明已显示提高治疗性间充质基质细胞对椎间盘的治疗效果的初步证据退化。为了进一步研究新水凝胶材料作为细胞载体的治疗用途，目前的研究旨在研究工作机制并优化处理椎间盘的配方变性和相关的下背痛。因此，设计了针对的特定研究研究水凝胶对治疗供体的表型稳定性和细胞因子释放的影响细胞，宿主椎间盘细胞的生物合成变化，响应于递送的供体细胞以及对治疗作用对使用多个体外和体内模型的实验动物中的椎间盘退化。本研究将生成可靠的概念数据证明，以便在治疗中使用肽官能化水凝胶用于椎间盘变性和相关下背痛治疗的治疗细胞的递送。