Enhanced Stem Cell Therapy with Rehabilitation Strategies for Peripheral Nerve Regeneration

项目摘要 超过10万例周围神经损伤(PNI)，包括机动车辆和战斗 美国和欧洲每年都会发生事故。此外，PNI占比近1- 第四例为儿科神经损伤。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。大多数患者会留下终生残疾和功能缺陷， 造成了重大的个人和社会负担。当前的黄金标准是使用 患者自体神经从一处切取修复损伤时的神经缺损(&gt；10 mm) 地点。然而，缺点很大，包括捐赠者的可获得性有限。 神经、供体神经的大小，以及手术部位的疤痕和并发症。 最近，人类神经干细胞(HNSCs)已经成为一种潜在的治疗方法。 用来恢复神经。然而，移植物立即存活率有限(5-20%)。 移植后因急性炎症/免疫反应，神经营养 因子退出，以及复杂微环境中的氧化应激。这 从而降低了hNSC治疗的疗效。这是至关重要的 了解移植的hNSCs如何受到其微环境线索的影响 维持它们的生存能力，并诱导所需的细胞行为，以加强神经修复。 干细胞通过生化因素与其微环境相互作用， 基质蛋白和细胞-细胞间的相互作用。我的研究重点是使用再生 生物物理、生化和生物电微环境战略，以进一步 增强移植的hNSCs的治疗潜力并维持其存活 修复神经缺陷。具体地说，将对hNSCs进行电刺激和封装 在硅纳米孔膜(SNM)，以提高治疗效果和存活率。 此外，还将实施身体康复，促进神经恢复。这个 本研究的目的是了解与周围神经相关的生物通路。 通过生化调节修复，并通过电和身体康复来 增强hNSCs的治疗潜力。通过了解两者之间的相互作用 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 可转化为更好的神经恢复和神经再生策略的途径 用于人类的PNI。

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.