Enhanced Stem Cell Therapy with Rehabilitation Strategies for Peripheral Nerve Regeneration

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、机动车事故以及肿瘤、血管和压迫有关 受伤每年约有1500亿美元用于神经损伤，其中87% 这些成本是由于医疗保健系统以外的生产损失。大多数病人都离开了 终身功能缺陷，造成重大的个人和社会负担。的 目前的黄金标准是使用患者自己的神经从一个位置， 损伤部位神经缺损。然而，缺点是显著的，包括有限的 供体神经的可用性，供体神经的大小，以及疤痕和并发症 发生在手术部位。近年来，人类神经干细胞（hNSCs） 作为一种潜在的神经恢复疗法然而，移植物存活率有限（5- 20%）由于急性炎症/免疫反应， 反应和神经营养因子撤退在复杂的微环境。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，我们可以研究新的设备 方法和识别可以转化为更好的神经恢复的基本途径 和人类PNI的神经再生策略。

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, motor vehicle accidents, as well as tumor, vascular, and compression injuries. Approximately $150 billion is spent each year because of nerve injury, with 87% of these costs due to lost production outside of healthcare system. Most patients are left with lifelong 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 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. 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 and neurotrophic factor withdrawal 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, 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.