关节软骨运动损伤修复中的骨形态发生蛋白

背景:骨形态发生蛋白是一种常用的组织工程支架材料,它在关节软骨损伤修复中起着不可替代的作用。目的:介绍关节软骨损伤修复的方法、骨形态发生蛋白的分类;重点阐述骨形态发生蛋白在运动性关节软骨损伤修复中的应用。方法:以"骨形态发生蛋白,运动损伤,关节软骨,修复"为中文检索词;以"bone morphogenetic protein,sports injuries,articular cartilage,repair"为英文检索词,应用计算机检索Pubmed数据库和维普数据库1998-01/2010-04的相关文章。纳入与骨形态发生蛋白关节软骨损伤修复研究相关的文献,排除重复性研究。结果与结论:共检索到74篇文献,排除无关重复的文献,保留20篇文献进行综述。目前研究证实骨形态发生蛋白具有强大的促成骨活性,能够诱导间充质细胞不可逆地分化为骨、软骨组织;但骨形态发生蛋白家族各成员诱导成骨作用的能力不同,其中骨形态发生蛋白2和骨形态发生蛋白7的成骨能力最强。同时相关研究表明骨形态发生蛋白对关节软骨损伤修复具有促进作用,但要将其应用于临床仍存在作用机制不明、复合材料的选择、应用于人体的安全性和有效性等问题。     

肌腱损伤的修复材料

背景：目前肌腱修复研究需要解决的问题很多,如肌腱缝合与粘连的机制研究,提高肌腱愈合质量研究,缝合材料与方法的改进,肌腱缝接处的抗张强度研究,组织工程肌腱的生物材料研究等,这些都是影响肌腱修复研究发展的重要问题。 目的：通过对汤森路透Web of Science数据库收录2002/2011有关肌腱损伤修复材料相关文献的献计量学分析,评估该领域学术文献的总体趋势,为该领域的深入研究提供参考。 设计：文献计量学分析。 资料提取：由第一作者以电子检索方式对汤森路透Web of Science数据库2002-01/2011-12肌腱损伤修复材料研究的文献进行分析,采用检索词为“tendon injury(肌腱损伤),material (材料),repair (修复)”,对检索的相关文献运用数据库中自带的分析功能和Excel软件绘制图表的功能进行分析,描述其分布特征。 入选标准：纳入经同行评议的肌腱损伤修复材料研究已发表的文献,包括研究原著、综述和会议的文献类型。排除：①需采用手工检索和电话检索方式收集的文章。②未正式出版的文章。③在收录数量之外排除勘误类文献类型。 主要数据的判定指标：以SCI数据库相关文献出版时间、文献的数量、学科分类、文献类型、发文量较多的作者、来源出版物、会议、发文量较多的机构、国家地区分布、基金资助情况、文献语种和被引频次进行分析。 结果：①汤森路透Web of Science数据库过去10年共收录肌腱损伤修复材料研究相关文献156篇。从文献发表数量的趋势上看,总体呈现出逐步上升的状态,2009年收录该领域的相关文献达到顶峰,为28篇。其中研究原著类文章共收录141篇,综述类文章13篇。研究文字的学科领域集中在骨科学和外科学方向,其次为运动科学和工程学。②目前发表量较多的出版物为American Journal of Sports Medicine《美国运动医学杂志》、Foot Ankle International《足与踝国际杂志》和Archives of Orthopaedic and Trauma Surgery《矫形外科与创伤外科学文献集》。发表文献的国家以美国为主,占全球相关领域发稿量的42.9%。中国在过去10年间被收录文章总量位居第5名,共发表9篇相关文章,占全球相关文章的5.8%。③肌腱损伤修复材料研究相关文献的基金以NIH资助为主。最高被引频次文章主要发表在Journal of Cellular Physiology《细胞生理学杂志》和Cytokine & Growth Factor Reviews《细胞分裂与生长因子评论》等期刊上。 结论：文献分析显示,近几年来肌腱损伤修复材料的研究趋于成熟,发文量稳定并且呈逐渐上升趋势,是目前骨科、外科和运动医学领域的研究热点。       

生物材料修复运动性肌肉肌腱损伤：2007/2009 CNKI数据库相关文献的评价

目的：文献分析当前生物材料在修复运动性肌肉肌腱损伤方面研究现状。 方法：以“生物材料、运动损伤、修复、肌腱”为中文关键词,采用计算机检索中国期刊论文数据库2007-01/2009-12相关文章。纳入关于生物材料在修复肌肉、肌腱方面研究的文章,排除重复研究或Meta分析类文章。以19篇文献为主,重点对生物材料在修复肌肉肌腱方面研究文献进行了整理分析。 结果：组织工程研究的不断深入为运动性肌肉肌腱损伤的修复提供了可靠的生物材料和技术保障,生物材料修复运动性肌腱损伤具有与人体组织相容性好、易被组织吸收、不易感染、无粘连及断裂、无排斥等现象,表现了其优势。同时人工生物材料的妥善运用,为肌腱损伤后的快速良好康复提供了可能及保障。 结论：肌腱愈合由内、外源愈合共同作用,以内源性愈合方式为主,同时又与腱鞘、腱纽及滑液等条件有密切联系;肌腱粘连多是由于外源性愈合参与过多及腱周损坏所致。     

关节软骨缺损的组织工程修复

背景：软骨组织工程主要由种子细胞、生物支架、生长因子3方面组成,如何完善软骨组织工程修复一直是科研工作者研究的重点。 目的：全面了解应用软骨组织工程修复软骨损伤的研究现状。 方法：计算机检索PubMed和CNKI数据库中2005/2010相关文献。以“Cartilage, tissue engineering, repair”或“关节软骨、组织工程、修复”为检索词进行检索。纳入与软骨组织工程密切相关的文献,排除重复性研究。 结果与结论：共检索到167篇文献,排除无关重复的文献,保留20篇文献进行综述。研究认为种子细胞是软骨组织工程最关键的方面,包括软骨细胞、骨髓间充质干细胞、胚胎干细胞和通过基因工程得到的种子细胞。目前应用最多、应用前景最好的是骨髓间充质干细胞。生物支架经历了一个漫长的过程,趋向于复合性和功能性的方向发展。各种生长因子在组织工程中必不可少。转化生长因子、胰岛素样生长因子、骨形态发生蛋白等在软骨修复中发挥了重要的功能。     

成体干细胞与肺重建

背景：肺组织结构复杂,病变周期长,具有主动归巢与调控功能的干细胞植入的治疗手段具有巨大的应用前景。 目的：全面了解成体干细胞治疗肺疾病与损伤的研究进展。 方法：由第一作者检索Pubmed数据库中2011年前发表的有关成体干细胞与肺损伤,多系分化及组织重建等方面的文章,排除重复性研究。 结果与结论：共检索到135篇相关文献,保留其中50篇进行综述。研究表明以骨髓来源的间充质干细胞为代表的成体干细胞具有较强的多系分化潜能,可用于治疗肺部疾病,可参与损伤修复甚至组织再生。其治疗机制及相关影响因素还有待进一步研究。     

嗅鞘细胞移植治疗脊髓损伤：问题与瞻望

背景：嗅鞘细胞兼具有许旺细胞和星形胶质细胞的特性,能分泌多种神经生长因子和营养因子,改善脊髓损伤局部的微环境、诱导轴突的再生及髓鞘化、促进脊髓损伤后的功能恢复。 目的：总结当前嗅鞘细胞移植治疗脊髓损伤的最新研究成果,将研究思路和最新研究进展相结合进行综述。 方法：以“olfactory ensheathing cell,transplantation,spinal cord injury”为检索词,检索PubMed数据库(1990-01/2012-01),以“嗅鞘细胞,移植,脊髓损伤”为检索词,检索CNKI数据库(2000-01/2012-01),文献检索语种为英文和中文。纳入与嗅鞘细胞移植治疗脊髓损伤相关的文献,排除重复文献。 结果与结论：计算机初检得到372篇文献,根据纳入排除标准,对其中23篇文献进行分析。大量动物及临床实验研究表明,嗅鞘细胞移植能有效促进脊髓损伤局部形态及功能的恢复,为临床治疗脊髓损伤患者提供了新途径。但是如何解决嗅鞘细胞的来源问题、如何避免异体移植免疫排斥反应的发生、以及异种移植中的生物安全问题是限制嗅鞘细胞移植治疗脊髓损伤临床应用的重要因素。因此,自体嗅鞘细胞移植治疗脊髓损伤能够较好地解决上述问题,将有可能成为后续研究的热点。     

微管相关蛋白2与脊髓发育和损伤的修复

背景：微管相关蛋白2作为神经元特异性标记蛋白之一,其表达活性在一定程度上反映了脊髓神经细胞增殖、分化、迁移的演变规律。 目的：综述微管相关蛋白2的分子结构、生物学功能及其在脊髓发育及损伤修复中的表达分布规律,进而为脊髓损伤后神经干细胞的移植治疗提供前期研究基础。 方法：应用计算机检索1984/2012 维普、万方数据库相关文章,检索词为“脊髓,微管相关蛋白2”。同时计算机检索1984/2012 PubMed和Springer外文电子期刊及电子图书(全文)数据库相关文章,检索词为“spinal cord,Microtubule-associated protein 2(MAP-2)”。共检索到文献325篇,最终纳入符合标准的文献27篇。 结果与结论：微管相关蛋白2不仅是神经细胞的骨架成分,更是一种活跃的功能蛋白,参与神经元的生长和损伤后的修复过程,它的表达强弱可以反映脊髓神经元的发育情况。微管相关蛋白2免疫活性下降在脊髓损伤中的作用日益受到重视,而它的高表达可能在脊髓损伤后突触结构重建及受损神经功能代偿和修复中发挥重要作用。通过检测微管相关蛋白2的含量和定位,可以用来研究人类多种神经干细胞增殖、分化、迁移规律,进而探索脊髓等中枢神经系统的发育和损伤修复状况。     

间充质干细胞生物学特性研究现状

背景：间充质干细胞在组织修复方面的作用已有大量报道,最近还发现其具有免疫调节功能,但对于其发挥作用的具体途径仍不够清楚。 目的：讨论间充质干细胞发挥免疫调节作用的机制。 方法：由第一作者应用计算机检索PubMed数据库2000/2010有关间充质干细胞在组织损伤后的归巢特性及发挥免疫调节功能机制的文献。检索词为“mesenchymal stem cells,tissue repairing,homing,immunomodulatory”,限定文章语言种类为English,检索文献包括研究原著及综述,排除重复性研究。 结果与结论：共保留50篇文献归纳总结。间充质干细胞参与组织损伤修复的作用已被证实,最近发现其还具有免疫调节功能,作用的相关机制多效而复杂,多种因子介导的腺体-受体反应及相关免疫细胞参与此过程。间充质干细胞免疫调节作用的相关机制仍不完全明确,需要进一步的研究来证实及完善。     

人工合成材料在膝交叉韧带损伤修复中的应用

目的:通过对人工合成材料重建膝交叉韧带研究进展的研究和临床实验观察,着重探讨其重建后在损伤修复中的应用前景。方法:由第一作者应用计算机检索维普数据库与人工合成材料重建膝交叉韧带有关的文献,检索时限为1993-01/2009-10。检索关键词:膝关节交叉韧带;人工韧带;移植重建。纳入标准:①人工合成材料在膝交叉韧带损伤修复中应用等相关文献。②LARS人工韧带重建膝前、后交叉韧带的实验研究与临床应用相关的文章。排除标准:③排除较陈旧的理论观点以及一些重复性研究。对资料进行初审,并查看每篇文献后的引文。结果:计算机初检到105篇文献,阅读标题和摘要进行初筛,排除研究目的与本文无关的文献40篇,内容重复性研究44篇,共21篇文献符合标准。膝关节前交叉韧带断裂是一种严重的膝关节损伤,可导致膝关节不稳,并可继发关节内主要结构损伤,严重影响关节功能。对于要求锻炼的年轻患者,特别是运动员前交叉韧带损伤,LARS人工韧带是理想移植材料。目前为止,LARS人工韧带的并发症报道比例较小,特别是没有滑膜炎的报道,被认为是安全的移植材料。结论:人工韧带为前、后交叉韧带重建的确提供了一种选择,但仍存在不足之处,还不是最理想的移植物,也不能完全代替交叉韧带。     

周围神经端侧缝合修复神经缺损的研究与应用

背景：神经端侧缝合对治疗神经近端回缩或撕脱消失的神经损伤有明显的优点,无需考虑受损神经近端缺损距离的大小,不影响供体神经的功能。 目的：总结端侧缝合修复周围神经的科研与临床领域方面的研究,为修复周围神经缺损,特别是神经缺损较长、近端无法寻找而不能做端端缝合时,提供一种可供选择的途径。 方法：由第一作者应用计算机检索PubMed和万方数据库1990-01/2010-10发表的相关文献。以“end-to-side neurorrhaphy or end-to-side coaptation , nerve repair”或“神经端侧缝合或神经端侧缝合,神经修复”为检索词进行检索。选择与神经端侧缝合修复周围神经损伤有关的文献,同一领域文献则选择近期发表及发表在权威杂志的文章。 结果与结论：共检索到86篇文献,排除无关重复的文献,保留38篇文献进行综述。目前认为是许旺细胞可诱导完整的供体神经轴突的侧突出芽,许旺细胞在吻合口处快速增生,并产生大量营养因子。神经外膜及束膜,在神经端侧缝合中起到屏障作用,可阻止新生的轴突长入神经断端。端侧缝合对损伤的周围神经为有效的修复方式,必要时可在临床上广泛应用。     

Prospective assessment of fetal-maternal cell transfer in miscarriage and pregnancy termination

BACKGROUND Fetal cells (microchimerism) are acquired by women during pregnancy. Fetal microchimerism persists decades later and includes cells with pluripotent capacity. Persistent microchimerism has the capacity for both beneficial and detrimental maternal health consequences. Both miscarriage and termination of pregnancy can result in fetal microchimerism. We sought to determine whether cellular fetal microchimerism is acquired during management of pregnancy loss and further explored factors that could influence fetal cell transfer, including viability of fetal tissue, surgical versus medical management and gestational age. METHODS Pregnant women (n= 150 samples from 75 women) with singleton pregnancies undergoing a TOP (n= 63) or treatment for embryonic or fetal demise (miscarriage, n= 12) were enrolled. Mononuclear cells were isolated from blood samples drawn before, and 30 min after, treatment. Fetal cellular microchimerism concentrations were determined using quantitative PCR for a Y chromosome-specific sequence, expressed as genome equivalents of fetal DNA per 100 000 maternal cell equivalents (gEq/10(5)). Detection rate ratios were determined according to clinical characteristics. RESULTS Cellular fetal microchimerism was found more often in post- compared with pretreatment samples, 24 versus 5% (P= 0.004) and at higher concentrations, 0-36 versus 0-0.7 gEq/10(5) (P< 0.001). Likelihood of microchimerism was higher in surgical than medical management, detection rate ratio 24.7 (P= 0.02). The detection rate ratio for TOP versus miscarriage was 16.7 for known male fetuses (P= 0.02). Microchimerism did not vary with gestational age. CONCLUSIONS Significant fetal cell transfer occurs during miscarriage and TOP. Exploratory analyses support relationships between obstetric clinical factors and acquisition of fetal cellular microchimerism; however, our limited sample size precludes definitive analysis of these relationships, and confirmation is needed. In addition, the long-term persistence and potential consequences of fetal microchimerism on maternal health merit further investigation.     

Fetal cells in maternal tissue following pregnancy: what are the consequences?

The presence and persistence of fetal cells in murine maternal tissue was first reported over 20 years ago, although it is only more recently that the occurrence and potential consequences of fetomaternal cell trafficking in humans have been fully appreciated. Fetal cell microchimerism is a growing field of investigation, although the data are contradictory relative to the health consequences of persistent fetal cells in maternal tissues. Understanding of the types of cells being transferred from fetus to mother, the location of these fetal cells within the various maternal tissue types, and the functionality of these cells may ultimately lead to measures to minimize or eliminate the deleterious effects of the cells, or to efforts to take advantage of the presence of these cells for therapeutic purposes. This review focuses on the origins of fetal cell microchimerism research and the different hypotheses regarding the consequences of persistent fetal cells in the mother, the various diseases that have been evaluated with respect to fetomaternal cell trafficking, the potential variables associated with the frequency, persistence and tissue distribution of fetal cells in maternal tissue, and an assessment of future direction in this innovative field of inquiry.     

Fetal microchimerism in human brain tumors

Sex differences in cancer incidence and survival, including central nervous system tumors, are well documented. Multiple mechanisms contribute to sex differences in health and disease. Recently, the presence of fetal‐in‐maternal microchimeric cells has been shown to have prognostic significance in breast and colorectal cancers. The frequency and potential role of these cells has not been investigated in brain tumors. We therefore selected two common primary adult brain tumors for this purpose: meningioma, which is sex hormone responsive and has a higher incidence in women, and glioblastoma, which is sex hormone independent and occurs more commonly in men. Quantitative PCR was used to detect the presence of male DNA in tumor samples from women with a positive history of male pregnancy and a diagnosis of either glioblastoma or meningioma. Fluorescence in situ hybridization for the X and Y chromosomes was used to verify the existence of intact male cells within tumor tissue. Fetal microchimerism was found in approximately 80% of glioblastoma cases and 50% of meningioma cases. No correlations were identified between the presence of microchimerism and commonly used clinical or molecular diagnostic features of disease. The impact of fetal microchimeric cells should be evaluated prospectively.     

Feto-maternal microchimerism in connective tissue diseases

Fetal progenitor cells traffic to the mother during pregnancy and can persist in the maternal circulation for many years. Feto-maternal microchimerism has been reported in women with scleroderma, but its contribution to the disease pathogenesis remains unclear. Furthermore, the involvement of microchimerism in other connective tissue diseases is controversial. We studied 243 females, 122 of whom had previously carried a male fetus (50 healthy controls, 23 patients with scleroderma, and 49 with other connective tissue diseases). The presence of the male-specific SRY sequence was analyzed using a kinetic quantitative ELISA PCR assay that allows detection of one to three male cells in one million female cells. The percentage of SRY-positive samples was not different among women having borne son(s): 16% (95% confidence interval 0.07-0.29) in healthy controls, 21.7% (0.07-0.44) in patients with scleroderma and 25.5% (0.14-0.40) in patients with connective tissue diseases (p=0.25). The mean number of fetal cells was similar in the three groups. Among the 121 females who never carried a male fetus, no healthy woman was SRY positive. However, 33% of patients with scleroderma and 22.9% of women with connective tissue diseases were chimeric, a phenomenon which might be related to early miscarriage(s). Therefore, feto-maternal microchimerism is a common event in both healthy controls and patients with connective tissue diseases, and is unlikely to represent per se a risk factor for these diseases.     

环境、材料、安全、可控：组织工程技术修复关节软骨的症结*

背景：传统的软骨缺损的修复方法都有其局限性,组织工程技术的出现从根本上改变了“以创伤修复创伤”的传统治疗模式。 目的：总结分析目前组织工程技术修复关节软骨的研究进展。 方法：由第一作者检索1990年至2011年 PubMed数据及中国知网数据库有关应用组织工程技术修复关节软骨方面的文献。共检索中文187 篇,英文211 篇,最终保留49篇进入结果分析。 结果与结论：软骨组织工程的主要方法就是应用工程学和生命科学原理,在体外分离、培养、扩增所需要的种子细胞,然后将之种植于合适的生物支架材料上,将细胞支架复合体植入体内组织缺损部位,并加入一定的诱导条件,逐渐形成新的有功能的软骨组织。文章在种子细胞的选择方面重点叙述了自体软骨细胞、异体软骨细胞、胚胎干细胞、骨髓间充质干细胞的研究进展;在细胞诱导及条件培养方面重点叙述了细胞因子、细胞条件培养、转基因技术的研究进展;并对生物支架材料的选择和研究进行了相关叙述。找到最理想的种子细胞,合理联合应用细胞因子,更加真实的模拟细胞生存的微环境,基因工程安全、高效、可控转染,构建理想的支架材料,将是今后组织工程研究的重点和热点。     

Maternal microchimerism—Allogenic target of autoimmune disease or Normal Biology?

Chimerism is the state of cells from two distinct individuals living within one body. Fetal cells pass into a mother during pregnancy, where they may persist at low levels for years, creating a state of fetal microchimerism. At the same time, maternal cells pass into the fetus, leading to maternal microchimerism that can persist into adulthood. Hematopoietic stem cell transplantation also creates a state of chimerism, and can lead to a complication of chronic multi-organ inflammation called graft-versus-host disease, (GVHD). The similarities between GVHD and some autoimmune diseases like scleroderma, lupus and myositis suggest that chimerism may be involved in the pathogenesis of both. Maternal and fetal microchimerism in the blood and in tissues have been associated with autoimmune diseases. However, many healthy individuals harbor maternal and fetal cells. Human and animal studies have begun to elucidate the mechanisms for normal tolerance to maternal and fetal microchimeric cells, and how this tolerance may be broken in states of chronic inflammatory disease.     

Microchimerism in recurrent miscarriage

Maternal-fetal cell exchange during pregnancy results in acquisition of microchimerism, which can durably persist in both recipients. Naturally acquired microchimerism may impact maternal-fetal interaction in pregnancy. We conducted studies to ask whether microchimerism that a woman acquired from her own mother is detectable before or during pregnancy in women with recurrent miscarriage. Fetal microchimerism was also assayed. Women with primary idiopathic recurrent miscarriage （n=23） and controls （n=31） were studied. Genotyping was conducted for probands, their mothers and the fetus, a non-shared polymorphism identified and quantitative polymerase chain reaction performed to measure microchimerismin peripheral blood mononuclear cells. Preconception comparisons were made between recurrent miscarriage subjects and controls, using logistic regression and Wilcoxon rank sum. Longitudinal microchimerism in subsequent pregnancies of recurrent miscarriage subjects was described. There was a trend toward lower preconception detection of microchimerism in recurrent miscarriage versus controls, 6% vs. 19% （1/16 vs. 6/31, P=0.2）. During pregnancy, 3111 （27%） of recurrent miscarriage subjects who went on to have a birth had detection of microchimerism from their own mother, whereas neither of two subjects who went on to miscarry had detection （0/2）. This initial data suggest that microchimerism from a woman＇s own mother, while detectable in women with recurrent miscarriage, may differ from controls and according to subsequent pregnancy outcome. Further studies are needed to determine the cell types,quantities and any potential functional role of microchimerism in recurrent miscarriage.     

干细胞移植与神经修复

背景：随着生命科学发展,利用干细胞来源的组织工程技术,有可能使受损的神经组织恢复再生能力。 目的：针对较为重要的几种干细胞在神经系统修复中的临床应用做一综述,以期阐明各自适用范围和临床效度,为临床医师按需选择提供参考。 方法：应用计算机检索PubMed 数据库中1998至2011年期间的关于干细胞移植在神经修复方面研究的文章,检索词为“Stem cells, Transplantation, Nerve repair”,限定语种为“English”。同时,检索万方数据库中2006至2011年期间的相关文章,检索词为“干细胞,移植,神经修复”,限定语种为中文。 结果与结论：初次检索得到288篇文章,选择与移植干细胞的来源、分化、特征及其在神经修复方面相关的文章,包括基础研究和临床研究,观察对象无论为人或动物,均进行审校。根据纳入标准,在排除重复和个案报道类文章之后,重点选择32篇文章进行综述。说明干细胞移植为神经系统疾病的治疗提供了一条新途径,使传统认为的不可修复、不可再生的神经组织的结构修复和功能重建成为可能。干细胞移植是一个全新的领域,还有许多问题亟待解决。     

内皮祖细胞生物学特征及其临床应用

背景：内皮祖细胞已经广泛用于研究缺血性疾病,能促进内皮再生、血管修复及组织中新生血管形成。 目的：综述内皮祖细胞生物学特征及其临床应用的研究进展。 方法：应用计算机检索1997-01/2010-12 PubMed数据库相关文章,检索词为“endothelial progenitor cells,ischemic cerebrovascular disease,early endothelial progenitor cells,late endothelial progenitor cells”,共检索到文献219篇,最终纳入符合标准的文献28篇。 结果与结论：内皮祖细胞定居于成体骨髓,现已证实胎肝、人脐血、成人外周血及骨髓中均存在,且人脐血、外周血中的内皮祖细胞均来源于骨髓。此外在心脏、血管、脂肪组织和骨骼肌等外周组织中也发现内皮祖细胞的存在。内皮祖细胞具有促进内皮再生及血管修复的功能,能促进组织中新生血管形成,在防治血管成形术后再狭窄等血管性疾病中发挥重要作用,其中晚期内皮祖细胞比早期内皮祖细胞更易形成毛细血管,在干细胞移植临床应用于缺血性脑卒中具有广泛的前景。