Enhanced Stem Cell Therapy with Rehabilitation Strategies for Peripheral Nerve Regeneration

增强干细胞治疗与周围神经再生康复策略

• 批准号: 9922117
• 负责人: Shang Song
• 金额: $ 7.01万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-27 至 2022-03-26
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9922117
• 关键词: Accidents; Acute; Adult; Animal Model; Biochemical; Biological; Biomedical Engineering; Biophysics; Birth; Blood Vessels; Brachial plexus structure; Cell Communication; Cell Differentiation process; Cell Membrane Permeability; Cell Survival; Cells; Child; Childhood; Cicatrix; Complex; Coupled; Cues; Defect; Devices; Effectiveness; Electric Stimulation; Electrophysiology (science); Encapsulated; Engineering; Europe; Exposure to; Fostering; Goals; Gold; Graft Survival; Harvest; Healthcare Systems; Human; Immune; Immune response; Implant; In Vitro; Infiltration; Inflammatory; Inflammatory Response; Injury; Knowledge; Left; Location; Longevity; Mediator of activation protein; Membrane; Methods; Modeling; Molecular Analysis; Motor Vehicles; Muscle; Muscular Atrophy; NTF3 gene; Nature; Nerve; Nerve Regeneration; Neurons; Neurotrophin 3; Operative Surgical Procedures; Oxidative Stress; Pathway interactions; Patients; Peripheral Nerves; Peripheral nerve injury; Physical Exercise; Physical Rehabilitation; Population; Process; Production; Proteins; Rattus; Recovery; Recovery of Function; Rehabilitation therapy; Research; Role; Silicon; Site; Spinal; Synapses; TNF gene; Techniques; Therapeutic; Training; Translating; Transplantation; Trauma; Withdrawal; Work; behavior test; bioelectricity; cell behavior; combat; cost; cytokine; disability; drug candidate; electrical potential; excitotoxicity; improved; in vivo; injury and repair; insight; nanopore; nerve injury; nerve stem cell; nerve supply; neuromuscular; neurotrophic factor; peripheral nerve regeneration; prevent; regenerative; rehabilitation strategy; relating to nervous system; release factor; repaired; response; sciatic nerve; stem cell therapy; stem cells; therapeutic effectiveness; treatment optimization; tumor; vehicular accident

Project Summary Over 100,000 peripheral nerve injuries (PNI) including motor vehicle and combat accidents occur annually in the U.S. and Europe. In addition, PNI accounts for nearly one- fourth of the pediatric nerve damage. Common causes in children include direct trauma related to birth (e.g. brachial plexus), motor vehicle accidents, as well as tumor, vascular, and compression injuries. In the U.S., approximately $150 billion is spent each year as a result of nerve injury, with 87% of these costs due to lost production outside of healthcare system. The majority of patients are left with lifelong disability and functional deficits, creating a major personal and societal burden. The current gold standard is to use a patient's own nerves harvested from one location to treat nerve defects (>10 mm) at injury site. However, the drawbacks are significant including the limited availability of the donor nerve, size of donor nerve, and scarring and complications occurring at the surgical sites. More recently, human neural stem cells (hNSCs) have emerged as a potential treatment for neural recovery. However, there is limited graft survival (5-20%) immediately following transplantation due to acute inflammatory/immune response, neurotrophic factor withdrawal, and oxidative stresses in the complex microenvironment. This subsequently diminishes the therapeutic effectiveness of hNSC therapy. It is crucial to understand how transplanted hNSCs are influenced by their microenvironmental cues to sustain their viability and elicit the desired cellular behaviors to enhance nerve repair. Stem cells interact with their microenvironment through biochemical factors, matrix proteins, and cell-cell interactions. My research focuses on using regenerative strategies to biophysical, biochemical, and bioelectrical microenvironment to further enhance the therapeutic potential and sustain the survival of transplanted hNSCs to repair nerve defects. Specifically, hNSCs will be electrically stimulated and encapsulated in silicon nanopore membrane (SNM) for enhanced therapeutic effectiveness and survival. In addition, physical rehabilitation will be implemented to promote nerve recovery. The goal of this research is to understand biological pathways related to peripheral nerve repair through biochemical modulation, and electrical and physical rehabilitation to enhance the therapeutic potential of hNSCs. By understanding the interplay between stem cells and various forms of rehabilitation strategies (e.g. electrical stimulation, physical exercise), we can investigate new device approaches and identify essential pathways that can translate into better neural recovery and nerve regeneration strategies for PNI in humans.

项目摘要 超过100，000例周围神经损伤（PNI），包括机动车和战斗 在美国和欧洲每年都有事故发生。此外，PNI占近1- 第四是小儿神经损伤。儿童的常见原因包括直接创伤 与出生（如臂丛神经）、机动车事故以及肿瘤、血管 和压迫性损伤在美国，每年约有1500亿美元用于 神经损伤的结果，其中87%的成本是由于医疗保健以外的生产损失 系统大多数患者留下终身残疾和功能缺陷， 造成重大的个人和社会负担。目前的黄金标准是使用 从一个位置采集患者自身神经，以治疗损伤处的神经缺损（>10 mm） 绝佳的价钱然而，缺点是显著的，包括供体的有限可用性 神经，供体神经的大小，以及手术部位的瘢痕和并发症。 最近，人类神经干细胞（hNSCs）已经成为一种潜在的治疗方法。 用于神经恢复然而，移植物存活率有限（5-20%）， 移植后由于急性炎症/免疫反应，神经营养 因子戒断和复杂微环境中的氧化应激。这 随后降低了hNSC疗法的治疗效果。至关重要 了解移植的hNSCs如何受到其微环境线索的影响， 维持它们的活力并引发所需的细胞行为以增强神经修复。 干细胞通过生化因子与微环境相互作用， 基质蛋白和细胞间相互作用。我的研究重点是利用再生能源 生物物理、生物化学和生物电微环境的策略， 增强治疗潜力并维持移植的hNSC的存活， 修复神经缺损具体地，将对hNSC进行电刺激并包封 在硅纳米孔膜（SNM），以提高治疗效果和生存。 此外，还将实施身体康复，促进神经恢复。的 本研究的目的是了解与周围神经相关的生物学通路 通过生物化学调节以及电气和物理康复进行修复， 增强hNSC的治疗潜力。通过理解 干细胞和各种形式的康复策略（例如电刺激， 体育锻炼），我们可以研究新的设备方法，并确定必要的 可以转化为更好的神经恢复和神经再生策略的途径 PNI在人类