干细胞移植与运动性颅脑损伤的修复

背景：目前临床上针对颅脑损伤，尤其是运动性颅脑损伤的治疗方法是当前研究的热点问题之一。干细胞具有自我更新能力强、多向分化潜能等特点对运动性颅脑损伤的治疗提供了广阔的应用前景。 目的：通过分析运动性颅脑损伤的病理学变化及干细胞技术的应用，探讨干细胞技术应用于运动性颅脑损伤，促进其功能恢复的重要作用。 方法：应用计算机检索Medline数据库(1994-01/2010-03)、重庆维普数据库(1994-01/2010-06)、清华同方数据库(1994-01/2010-06)等以“Stem cell，spots brain injury，neural stem cells，mesenchymal stem cells”为英文检索词，以“干细胞；运动性颅脑损伤；神经干细胞；骨髓间充质干细胞”为中文检索词。以与运动性颅脑损伤和干细胞技术相关的文献为纳入标准，以重复性研究、陈旧性文献为排除标准。共检索到126篇相关文献，通过对重复性研究和陈旧性研究之后得到23篇符合标准的文献。 结果与结论：干细胞移植技术应用于颅脑损伤的研究虽已取得了很大的进步，但在治疗运动性颅脑损伤的领域尚处于探索阶段，有待进一步研究解决的问题很多，通过分析发现干细胞尤其是神经干细胞和骨髓间充质干细胞对于运动性颅脑损伤的治疗具有十分重要的作用，且其研究前景较为广阔。     

干细胞与运动性骨骼肌细胞凋亡

背景：运动性骨骼肌细胞凋亡业已成为当前运动医学领域的研究重点,干细胞应用于运动性伤病的恢复和防治也有报道,但将干细胞用于细胞凋亡干预作用的相关研究还很少。 目的：总结干细胞防治运动性骨骼肌细胞凋亡的作用及其机制,为科学的运动训练和体育锻炼提供依据。 方法：通过计算机检索PubMed数据库1991-01/2009-10的相关文献,检索词为“Exercise Training,Sports,Skeletal Muscle,Apoptosis”,并限定文章语言种类为English。同时计算机检索中国期刊全文数据库1994-01/2009-10的相关文献,检索词“干细胞、运动、骨骼肌、细胞凋亡”,并限定文章语言种类为中文。纳入标准：①文章所述内容应与干细胞及其骨骼肌细胞凋亡的研究密切相关。②同一领域选择近期发表或在权威杂志上发表的文章。排除标准：①重复性研究。②Meta分析。 结果与结论：共检索到360篇文献,对资料进行初审,文献的来源主要是通过对干细胞及其在运动医学领域的研究进展,以及骨骼肌细胞凋亡的变化与发展趋势等的应用情况进行汇总分析,共选取31篇文献,其中21篇为综述,其余均为临床或基础实验研究。大强度的运动可引起骨骼肌细胞出现凋亡,而运用干细胞技术可在一定程度上起到预防细胞凋亡的作用,干细胞可通过调节Bcl-2和Bax蛋白表达来防治运动过程中出现的骨骼肌细胞凋亡,从而促进运动机体骨骼肌的早期恢复。     

运动医学领域周围神经损伤研究的特点与进展

研究发现周围神经损伤的病理病因主要表现在周围神经损伤的功能障碍。由于运动中不同项目的需求,易引起周围神经受到牵拉、截断、缺血和压迫等原因致使其周围神经组织出现退行性改变、假性神经瘤或神经截断等,而针对运动中所出现的周围神经损伤的这一病理机制,采取神经再生促肌肉功能恢复、复合物理疗法和功能康复等的方式能够在一定程度上防治和减轻周围神经损伤的出现。文章通过对周围神经损伤的生物学、运动性周围神经损伤的病理病因及其康复等的分析,旨在探讨运动性周围神经损伤的康复方法,为防治运动性周围神经损伤提供科学依据。     

骨髓间充质干细胞与运动性心肌细胞凋亡

背景：运动性心肌细胞凋亡及其信号转导和调节机制的研究已成为运动医学领域的重要课题，但其研究成果并未能成功的解释此种现象。从现有的研究成果来看，引入骨髓间充质干细胞对运动性心肌细胞凋亡保护作用的研究还较少。 目的：通过骨髓间充质干细胞对心肌细胞凋亡的保护作用以及运动引起心肌细胞凋亡现象的分析，探讨运动引起心肌细胞凋亡的病理病因，及骨髓间充质干细胞对保护机体心肌细胞因运动致使缺氧、缺血、氧化应激等诱导细胞凋亡的作用。 方法：应用计算机检索Medline数据库(1994-01/2009-09)，以Mesenchymal stem cells，Excessive exercise，Cardiomyocyte，Apoptosis为检索词；应用计算机检索重庆维普数据库(1994-01/2009-09)、清华同方数据库(1994-01/2009-06)，以骨髓间充质干细胞、过度训练、心肌细胞、细胞凋亡为检索词。 结果与结论：共收集365篇关于干细胞和运动性心肌细胞凋亡的文献，中文120篇，英文245篇。排除发表时间较早、重复及类似研究，纳入68篇符合标准的文献。骨髓间充质干细胞对大强度或超负荷的运动训练所引起的缺氧、缺血、氧化应激等诱导的心肌细胞凋亡有保护作用，从而促进心脏功能的提高和运动性心肌组织疾病的早期康复。     

电针治疗周围神经损伤的修复机制**

背景：多年来临床及实验研究表明,电针治疗对周围神经损伤修复有着肯定的效果,其相关机制也一直是针灸研究者关注的热点之一。 目的：总结电针治疗周围神经损伤的研究现状及其可能机制,以期更深入地探讨电针治疗周围神经损伤的机制,促进针灸临床疗效的提高。 方法：由第一作者应用计算机检索中国知识资源总库和Ovid数据库,检索词分别为“电针;周围神经”和“electro acupuncture;peripheral nerve regeneration”,语言分别设定为中文和英文。纳入所述内容与电针治疗对周围神经损伤修复的疗效及作用机制相关的文献,排除相关性较低、重复研究以及较陈旧的文献。 结果与结论：计算机初检得到138篇文献,阅读标题和摘要进行筛选,共纳入27篇符合标准的文献。经分析得出以下结论：电针是治疗周围神经损伤的有效方法。其治疗机制可通过生物电场作用、改善运动终板内的营养物质含量和结构、促进神经生长相关蛋白表达增多、促进神经营养因子3及其受体表达增多、增强神经生长因子-信使核糖核酸的表达以及促进许旺细胞的增殖等方面来促进周围神经损伤的修复。 关键词：电针;周围神经损伤;神经损伤修复;神经再生;综述文献。     

骨髓间充质干细胞与运动性膝关节损伤

背景：膝关节损伤是运动损伤中最常见的创伤之一，严重影响了运动员的训练和比赛，其损伤还可造成心血管和代谢的运动适应性减退和失用性肌萎缩。骨髓间充质干细胞以其多向分化潜能、低免疫原性、无排斥反应等优点为其在膝关节损伤的防治领域提供了广阔的应用前景。 目的：总结骨髓间充质干细胞作用于运动性膝关节损伤的应用，旨在为膝关节损伤的预防和治疗提供科学依据。 方法：通过计算机检索PubMed数据库检索1994-01/2010-05的文献资料，以“骨髓间充质干细胞、运动、膝关节损伤” 为中文检索词，以“mesenchymal stem cell，sports, knee injuries” 为英文检索词。纳入骨髓间充质干细胞和运动性膝关节损伤相关文献，排除重复性研究，共选取了34篇论文进行分析讨论。 结果与结论：通过对骨髓间充质干细胞的生理特性、临床应用以及运动性膝关节损伤的原因分析，探讨骨髓间充质干细胞对运动性膝关节软骨、肌腱、肌细胞和半月板损伤的修复作用。结果发现骨髓间充质干细胞以其取材方便、创伤小且易于从骨髓中分离等的优点为修复膝关节软骨损伤、促进其肌腱的修复和治疗膝关节半月板损伤等有极为重要的价值。     

许旺细胞在周围神经损伤修复中的作用及其可能分子机制**★

背景：周围神经损伤后神经功能的恢复一直是人们关注的焦点。许旺细胞在促神经功能恢复方面有着不可替代的作用。 目的：对国内外有关许旺细胞在促神经功能恢复方面的作用及其可能的分子机制作一综述。 方法：应用计算机检索CNKI、VIP和OVID数据库中1993-01/2010-01关于周围神经损伤的文章，在标题和摘要中以“许旺细胞，周围神经，神经再生，综述”或“Schwann Cells，Peripheral Nerve，Nerve Regeneration, Review”为检索词进行检索。选择文章内容与许旺细胞对周围神经损伤的作用有关者，同一领域文献则选择近期发表或发表在权威杂志上的文章。初检得到256篇文献，根据纳入标准选择关于许旺细胞作用机制的24篇文献进行综述。 结果与结论：许旺细胞通过多种途径作用于受损的周围神经，进而促进损伤神经功能的恢复。如何促使损伤局部许旺细胞更多的增殖将成为更好地促进损伤神经功能恢复的一大突破点。综合各方面因素，电针治疗周围神经损伤将有更好的前景。     

神经干细胞与运动性神经疾病

背景：神经干细胞以其所具有的多向分化潜能、自我更新、迁徙性、低免疫性等特点受到临床的广泛应用，但有关神经干细胞在运动医学领域用于防治运动性损伤等的研究成果不是很多。 目的：旨在通过分析神经干细胞的生物学特性，探讨其在临床上的应用，为神经性疾病的预防和治疗提供理论依据。 方法：应用计算机检索CNKI和PubMed数据库中1997-01/2010-10关于神经干细胞与运动性神经疾病的文章，在标题和摘要中以“神经干细胞，运动医学，失神经肌萎缩，周围神经损伤”或“Neural Stem Cell，Sports Medicine，Denervation Muscle Atrophy，Peripheral Nerve Injury”为检索词进行检索，选择文章内容与神经干细胞和运动性神经疾病相关，同一领域文献选择近期发表或发表在权威杂志上的文章，初检得到262篇文献，根据纳入标准选择31篇进行综述。 结果与结论：神经干细胞以其多向分化潜能、自我维持和更新、低免疫原性、迁徙性和来源广泛等特点为其在治疗神经退行性病变、运动性骨骼肌失神经肌萎缩和促运动性周围神经损伤的再生等提供了较为广阔的应用前景，但由于基础性研究所限，对其作用机制、诱导分化、迁移等仍有待大量的实验研究予以证实。     

神经干细胞转基因疗法与运动性脊髓损伤的治疗

背景：神经干细胞基因疗法的提出,给运动性脊髓损伤的修复与治疗提供了广阔的应用前景和挑战。 目的：综述神经干细胞的增殖分化和基因调控促进运动性脊髓损伤恢复的效果。 方法：应用计算机检索Medline数据库、维普数据库和清华同方数据库1991-01/2010-12有关神经干细胞疗法治疗运动性脊髓损伤的文献,以“neural stem cells, gene therapy, exercise spinal cord injury, gene modification, gene transfection”为英文检索词,以“神经干细胞,脊髓损伤,基因治疗”为中文检索词,排除重复性、陈旧性研究,对所得文献资料进行整理,运用归纳演绎等方法进行分析。 结果与结论：神经干细胞的基因治疗能够通过其神经营养因子的修饰、增殖分化和移植技术,以替代坏死、凋亡的神经细胞,并在损伤区域分泌大量的神经营养因子,达到改善局部微环境,促进神经通路的重建、新生神经元的增殖等促进运动性脊髓损伤的再生与修复。同时,神经干细胞基因治疗运动性脊髓损伤还面临着巨大的考验,包括神经干细胞基因治疗技术的成熟性、转基因后的稳定高效表达性等相关问题还没有得到很好的解决,仍需要不断的进行基础性研究和临床实验。     

甲壳素类神经导管修复周围神经的研究与进展★

目的：概述近年来甲壳素类材料制备神经导管修复周围神经损伤的研究进展。 资料来源：应用计算机检索Medline和Springerlink 2000-01/2009-08有关神经导管材料修复周围神经损伤方面的文献，检索词“nerve conduit,peripheral nerve injury”，限定文献语言种类为“English”；同时检索中国期刊全文数据库、重庆维普数据库2000-01/2009-08相关文献，检索词“神经导管，周围神经损伤”，限定文章语言种类为中文。 资料选择：纳入与修复周围神经损伤有关的非生物降解材料、生物降解材料和生物衍生材料的文献。对资料进行初审，选取符合甲壳素类神经导管材料修复周围神经损伤要求的有关文章。排除标准相关度不大和重复性文章。 结局评价指标：神经组织工程；甲壳素类神经导管材料；神经导管制备。 结果：①随着医学材料的进展，天然或人工合成材料的神经导管用于桥接神经缺损的组织工程支架材料，具有引导和促进神经再生作用。生物可降解材料中甲壳素类神经导管可在合理的时间段内降解，有可控的生物亲和性、降解性能、多孔性和机械性能。②在导管结构、复合其他生物可降解材料、表面修饰、添加种子细胞及神经生长因子等方面进行实验研究。③通过改变再生室的空间结构和微环境，从而加快神经生长速度，促进神经功能的良好恢复。并对材料表面修饰及制备方法加以改进，使得导管适应神经再生。 结论：随着生物学技术和其他相关技术的发展，甲壳素类神经导管材料在周围神经组织工程中的应用必将得到不断的展现。 关键词：神经导管；甲壳素；生物可降解；周围神经损伤 doi:10.3969/j.issn.1673-8225.2009.47.027     

Roles of neural stem cells in the repair of peripheral nerve injury

Currently, researchers are using neural stem cell transplantation to promote regeneration after peripheral nerve injury, as neural stem cells play an important role in peripheral nerve injury repair. This article reviews recent research progress of the role of neural stem cells in the repair of peripheral nerve injury. Neural stem cells can not only differentiate into neurons, astrocytes and oligodendrocytes, but can also differentiate into Schwann-like cells, which promote neurite outgrowth around the injury. Transplanted neural stem cells can differentiate into motor neurons that innervate muscles and promote the recovery of neurological function. To promote the repair of peripheral nerve injury, neural stem cells secrete various neurotrophic factors, including brain-derived neurotrophic factor, fibroblast growth factor, nerve growth factor, insulin-like growth factor and hepatocyte growth factor. In addition, neural stem cells also promote regeneration of the axonal myelin sheath, angiogenesis, and immune regulation. It can be concluded that neural stem cells promote the repair of peripheral nerve injury through a variety of ways.     

Mesenchymal stem cell treatment for peripheral nerve injury: a narrative review

Peripheral nerve injuries occur as the result of sudden trauma and lead to reduced quality of life.The peripheral nervous system has an inherent capability to regenerate axons.However,peripheral nerve regeneration following injury is generally slow and incomplete that results in poor functional outcomes such as muscle atrophy.Although conventional surgical procedures for peripheral nerve injuries present many benefits,there are still several limitations including scarring,difficult accessibility to donor nerve,neuroma formation and a need to sacrifice the autologous nerve.For many years,other therapeutic approaches for peripheral nerve injuries have been explored,the most notable being the replacement of Schwann cells,the glial cells responsible for clearing out debris from the site of injury.Introducing cultured Schwann cells to the injured sites showed great benefits in promoting axonal regeneration and functional recovery.However,there are limited sources of Schwann cells for extraction and difficulties in culturing Schwann cells in vitro.Therefore,novel therapeutic avenues that offer maximum benefits for the treatment of peripheral nerve injuries should be investigated.This review focused on strategies using mesenchymal stem cells to promote peripheral nerve regeneration including exosomes of mesenchymal stem cells,nerve engineering using the nerve guidance conduits containing mesenchymal stem cells,and genetically engineered mesenchymal stem cells.We present the current progress of mesenchymal stem cell treatment of peripheral nerve injuries.     

Role of stem cells in the regeneration and repair of peripheral nerves

Peripheral nerve regeneration is a complex process, with Wallerian degeneration the most elementary reaction and Schwann cells playing an important role. In recent years, stem cells have been widely used to repair injured peripheral nerves. The sources of these stem cells are widespread and their effectiveness in the treatment of peripheral nerve injury may lie in their ability to differentiate into Schwann cells, secrete neurotrophic factors, and assist in myelin formation. Stem cells have been used as seed cells in tissue-engineered nerve grafts. The understanding of stem cell homing, novel repair material, and the ability to mobilize endogenous stem cells to assist peripheral nerve regeneration constitute a research direction of great interest.     

Stem-cell–based therapies to enhance peripheral nerve regeneration

Peripheral nerve injury remains a major cause of morbidity in trauma patients. Despite advances in microsurgical techniques and improved understanding of nerve regeneration, obtaining satisfactory outcomes after peripheral nerve injury remains a difficult clinical problem. There is a growing body of evidence in preclinical animal studies demonstrating the supportive role of stem cells in peripheral nerve regeneration after injury. The characteristics of both mesoderm-derived and ectoderm-derived stem cell types and their role in peripheral nerve regeneration are discussed, specifically focusing on the presentation of both foundational laboratory studies and translational applications. The current state of clinical translation is presented, with an emphasis on both ethical considerations of using stems cells in humans and current governmental regulatory policies. Current advancements in cell-based therapies represent a promising future with regard to supporting nerve regeneration and achieving significant functional recovery after debilitating nerve injuries.     

Impaired regeneration of bcl-2-lacking peripheral nerves

OBJECT: The outcome of peripheral nerve damage in still not satisfactory, despite the general capacity of peripheral nervous system to regenerate. The molecular mechanisms underlying nerve regeneration are still not clear, but it is likely that apoptosis regulating genes plays a crucial role in these processes. The aim of the present study was to establish the role of the anti-apoptotic gene bcl-2 in peripheral nerve repair. MATERIAL AND METHODS: Sciatic nerves of bcl-2-deficient and wild type mice were transected, and immediately re-sutured. The regeneration was assessed functionally and morphologically throughout the 4-week follow-up. RESULTS: We found markedly worse sciatic function index outcome, as well as more significant atrophy of denervated muscles in bcl-2 knock-out animals when compared with wild-type ones. The intensity of histological regeneration features, including GAP-43-positive growth cones, Schwann cells and macrophages in the distal stump of the transected nerve, was also decreased. The number of motor and sensory neurons in the relevant cross-sections of spinal cord was similar in both groups of mice. CONCLUSION: We concluded that the bcl-2 gene plays an important role in peripheral nerve regeneration, influencing nerve injury site clearing, fiber regrowth and myelination.     

LncRNA BC088259 promotes Schwann cell migration through Vimentin following peripheral nerve injury

Schwann cell, the major glial cell in the peripheral nervous system, plays an essential role in peripheral nerve regeneration. However, the regulation of Schwann cell behavior following nerve injury is insufficiently explored. According to the development of high-throughput techniques, long noncoding RNAs (lncRNAs) have been recognized. Accumulating evidence shows that lncRNAs take part in diverse biological processes and diseases. Here, by microarray analysis, we identified an upregulated lncRNA profile following sciatic nerve injury and focused on BC088259 for further investigation. Silencing or overexpression of BC088259 could affect Schwann cell migration. Mechanistically, BC088259 might exert this regulatory role by directly binding with Vimentin. Collectively, our study not only revealed a set of upregulated lncRNAs following nerve injury but also identified a new functional lncRNA, BC088259, which was important for Schwann cell migration, providing a therapeutic avenue toward peripheral nerve injury.     

Progesterone and peripheral nerve regeneration

IN T R O D U C T IO NVarious factors are involved in the process of regeneration after pe- ripheralnerve injury, including the m icroenvironm entofregeneration, neurotrophic factor, horm ones, etc. R ecent studies have found that progesterone plays an im …     

Role of adipose tissue grafting and adipose-derived stem cells in peripheral nerve surgery

The application of autologous fat grafting in reconstructive surgery is commonly used to improve functional form. This review aims to provide an overview of the scientific evidence on the biology of adipose tissue, the role of adipose-derived stem cells, and the indications of adipose tissue grafting in peripheral nerve surgery. Adipose tissue is easily accessible through the lower abdomen and inner thighs. Non-vascularized adipose tissue grafting does not support oxidative and ischemic stress, resulting in variable survival of adipocytes within the first 24 hours. Enrichment of adipose tissue with a stromal vascular fraction is purported to increase the number of adipose-derived stem cells and is postulated to augment the long-term stability of adipose tissue grafts. Basic science nerve research suggests an increase in nerve regeneration and nerve revascularization, and a decrease in nerve fibrosis after the addition of adipose-derived stem cells or adipose tissue. In clinical studies, the use of autologous lipofilling is mostly applied to secondary carpal tunnel release revisions with promising results. Since the use of adipose-derived stem cells in peripheral nerve reconstruction is relatively new, more studies are needed to explore safety and long-term effects on peripheral nerve regeneration. The Food and Drug Administration stipulates that adipose-derived stem cell transplantation should be minimally manipulated, enzyme-free, and used in the same surgical procedure, e.g. adipose tissue grafts that contain native adipose-derived stem cells or stromal vascular fraction. Future research may be shifted towards the use of tissue-engineered adipose tissue to create a supportive microenvironment for autologous graft survival. Shelf-ready alternatives could be enhanced with adipose-derived stem cells or growth factors and eliminate the need for adipose tissue harvest.Key Words: adipose tissue, adipose-derived stem cells, angiogenesis, autologous fat grafting, nerve injury, nerve regeneration, paracrine environment, peripheral nerve reconstruction, stem cell secretome, tissue engineering     

The interaction of stem cells and vascularity in peripheral nerve regeneration

The degree of nerve regeneration after peripheral nerve injury can be altered by the microenvironment at the site of injury. Stem cells and vascularity are postulated to be a part of a complex pathway that enhances peripheral nerve regeneration; however, their interaction remains unexplored. This review aims to summarize current knowledge on this interaction, including various mechanisms through which trophic factors are promoted by stem cells and angiogenesis. Angiogenesis after nerve injury is stimulated by hypoxia, mediated by vascular endothelial growth factor, resulting in the growth of preexisting vessels into new areas. Modulation of distinct signaling pathways in stem cells can promote angiogenesis by the secretion of various angiogenic factors. Simultaneously, the importance of stem cells in peripheral nerve regeneration relies on their ability to promote myelin formation and their capacity to be influenced by the microenvironment to differentiate into Schwann-like cells. Stem cells can be acquired through various sources that correlate to their differentiation potential, including embryonic stem cells, neural stem cells, and mesenchymal stem cells. Each source of stem cells serves its particular differentiation potential and properties associated with the promotion of revascularization and nerve regeneration. Exosomes are a subtype of extracellular vesicles released from cell types and play an important role in cell-to-cell communication. Exosomes hold promise for future transplantation applications, as these vesicles contain fewer membrane-bound proteins, resulting in lower immunogenicity. This review presents pre-clinical and clinical studies that focus on selecting the ideal type of stem cell and optimizing stem cell delivery methods for potential translation to clinical practice. Future studies integrating stem cell-based therapies with the promotion of angiogenesis may elucidate the synergistic pathways and ultimately enhance nerve regeneration.