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1.
背景:血清肿瘤坏死因子α和白细胞介素1β作为炎症递质,其水平与骨性关节炎病情相关。而骨髓间充质干细胞治疗骨性关节炎报道较少。 目的:用骨髓间充质干细胞治疗兔早期骨性关节炎,观察关节软骨T2值及血清肿瘤坏死因子α和白细胞介素1β水平并进行分析。 方法:将36只新西兰大白兔随机均分成对照组、模型组和治疗组。模型组兔仅建立骨性关节炎模型,治疗组在造模后第4周左膝关节腔内注射骨髓间充质干细胞;对照组膝关节腔内注射等量生理盐水。分别在治疗后第2周,1,2,3个月行左后膝关节核磁共振及血清肿瘤坏死因子α和白细胞介素1β水平检查。 结果与结论:与模型组比较,治疗组T2值降低,无关节腔积液;血清肿瘤坏死因子α和白细胞介素1β水平降低;软骨T2值变化与二者呈正相关。MRI能够反映早期关节软骨的生物学改变,可用于评价骨性关节炎治疗前后的改变;骨髓间充质干细胞在关节腔内可向软骨分化,为早期骨性关节炎患者提供了一种新的有效疗法。  相似文献   

2.
背景:大量的研究报道证明滑膜间充质干细胞在细胞形态、免疫表型、集落形成能力和分化潜能等方面与骨髓间充质干细胞相似,但在向软骨分化的能力上,滑膜间充质干细胞明显优于骨髓间充质干细胞。 目的:探讨滑膜间充质干细胞作为半月板软骨组织工程种子细胞的可行性。 方法:通过有限稀释单克隆培养法将滑膜间充质干细胞从兔滑膜组织中分离出来并加以纯化,在体外培养条件下对其形态学、超微结构、分子表型、增殖动力学、核型以及致瘤性等进行分析。 结果与结论:从兔滑膜细胞中分离纯化出滑膜间充质干细胞,体外单层培养具有极强的增殖能力,在第6天时达到生长的最高峰,倍增时间为(30.2±2.4) h。流式细胞术检测滑膜间充质干细胞表达间充质干细胞一些分子标记CD44、CD90。DNA含量检测、染色体核型分析、荷瘤实验结果表明,分离纯化的滑膜间充质干细胞是正常的二倍体细胞,无致瘤性,因此可作为半月板组织工程的种子细胞。  相似文献   

3.
目的:探索鸡卵蛋白诱导性兔类风湿性关节炎模型在早期关节中的应用,并评估超声引导下AIA模型关节腔穿刺活检,在活体中连续动态地获取病理标本的可行性、安全性。方法:将25只新西兰大白兔卵蛋白诱导的类风湿性关节炎组(AIA组)20只,对照组5只。在造模后高频超声分别观察超声影像特点。以ELISA法检测VEGF和TNF-α水平。在4、8、12、15周,超声引导下活检,获取滑膜病理,制作病理切片,镜下观察病理改变。结果:(1)模型各时间观测点测量的AIA组滑膜厚度、VEGF、TNF-α均高于对照组基线水平,具有显著性差异(P0.05)。(2)关节炎模型4周至8周期间,以病理学评分作为金标准,滑膜厚度、VEGF、TNF-α结果与病理学评分具有相关性。(3)超声引导下滑膜活检成功率为95%,术后无感染、出血、关节骨质损伤的情况。结论:(1)卵清蛋白诱导的兔类风湿关节炎模型可作为观察早期(8周前)关节炎病理生理改变的研究模型。(2)超声引导下的滑膜活检,可有效安全地获取病理标本。  相似文献   

4.
背景:传统的干细胞标记方法常需要病理组织学等侵袭性手段检测,无法动态观察整个实验过程,也不适合临床研究。 目的:观察超顺磁性氧化铁纳米颗粒体外标记对兔骨髓间充质干细胞生物学特性的影响以及标记兔骨髓间充质干细胞的体外MRI成像特征。 方法:采用红细胞裂解贴壁法培养扩增兔骨髓间充质干细胞。采用不同浓度超顺磁性氧化铁纳米颗粒(100,50,25,12.5 mg/L)联合多聚赖氨酸(0.75 mg/L)标记兔骨髓间充质干细胞。对标记兔骨髓间充质干细胞进行MRI检测,观察其成像特征。 结果与结论:25 mg/L的超顺磁性氧化铁纳米颗粒联合0.75 mg/L多聚赖氨酸标记兔骨髓间充质干细胞具有较好的安全性和有效性。此浓度对细胞的生长活性没有影响,不影响骨髓间充质干细胞的成骨成脂分化能力。MRI扫描在T2*WI序列上能明显有效地显像超顺磁性氧化铁纳米颗粒标记的兔骨髓间充质干细胞。 关键词:超顺磁性氧化铁纳米颗粒;骨髓间充质干细胞;标记;磁共振;安全性 doi:10.3969/j.issn.1673-8225.2012.06.001  相似文献   

5.
背景:通过细胞移植重建损伤脑组织成为治疗脑梗死的新途径,骨髓间充质干细胞成为近年来细胞移植治疗领域的重要种子细胞之一。 目的:探讨灯盏细辛注射液联合骨髓间充质干细胞移植对急性脑梗死大鼠S100B蛋白及超氧化物歧化酶表达的影响。 方法:采用线栓法制作大鼠急性脑梗死模型,建模成功后将80只SD大鼠随机分为对照组、灯盏细辛组、骨髓间充质干细胞组及联合组。分别于治疗前后用酶联免疫法检测各组大鼠血清S100B蛋白水平,黄嘌呤氧化酶法检测各组大鼠血清超氧化物歧化酶的表达;通过NIHSS神经功能评分观察模型大鼠的神经行为学变化,通过TTC染色测定脑梗死体积。 结果与结论:在治疗后第3,7,14天,灯盏细辛组、骨髓间充质干细胞组的S100B蛋白水平明显低于对照组,但高于联合组,差异有显著性意义(P < 0.05);灯盏细辛组、骨髓间充质干细胞的超氧化物歧化酶表达水平明显高于对照组,低于联合组,差异有显著性意义(P < 0.05);治疗后第1,2,3周各组的NIHSS神经功能评分比较,联合组<灯盏细辛组及骨髓间充质干细胞组<对照组,差异有显著性意义(P < 0.05);在治疗后2周联合组的脑梗死体积明显小于灯盏细辛组及骨髓间充质干细胞组,灯盏细辛组及骨髓间充质干细胞组又明显小于对照组,差异有显著性意义(P < 0.05)。结果表明灯盏细辛注射液联合骨髓间充质干细胞移植能够抑制急性脑梗死大鼠S100B蛋白表达,提高超氧化物歧化酶活性,从而起到脑保护作用。 中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程  相似文献   

6.
背景:膝关节软骨损伤后很难愈合,是临床上亟需解决的重要课题。目的:总结滑膜间充质干细胞在膝关节软骨损伤治疗上的优越性。方法:用英文主题词“Knee Joint, Cartilage, Synovial Membrane, Tissues, Injuries, Repair”在PubMed数据库中检索2005年8月至2015年8月文献总共625篇。采纳并分析滑膜间充质干细胞治疗膝关节软骨损伤文献48篇。排除其他非滑膜间充质干细胞及非膝关节软骨损伤治疗的相关文章,保留35篇文章进行综述。结果与结论:应用滑膜间充质干细胞治疗膝关节软骨损伤,能够获得更加理想的治疗效果,损伤组织本身固有的间充质干细胞是修复损伤组织的最佳种子细胞。中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程  相似文献   

7.
背景:近年来有关影响软骨和软骨下骨组织再生的炎症因子、生长因子以及力学负荷已有许多报道,但对骨关节炎整体发生机制还欠缺全面地了解。 目的:探讨骨关节炎患者骨髓间充质干细胞功能状态与病情进展的相关性。 方法:抽取股骨颈骨折患者、轻度及重度骨性关节患者股骨骨髓,贴壁法分离培养出骨髓间充质干细胞,采用CCK-8法检测各组患者骨髓间充质干细胞的增殖能力,取第3代骨髓间充质干细胞成软骨诱导培养2周后进行甲苯胺蓝染色。 结果与结论:从各组患者骨髓中均培养出骨髓间充质干细胞,对照组细胞的增殖能力明显高于轻度骨性关节炎组、重度骨性关节炎组;成软骨诱导分化后骨髓间充质干细胞形态发生明显改变,由长梭形逐渐变为类圆形或多角形,核浆比例明显减小,诱导细胞甲苯胺蓝染色阳性。重度骨性关节炎组诱导出的软骨细胞的数量少于对照组,但细胞形态差异不大。结果表明骨性关节炎的发生与自身的骨髓间质干细胞的功能形态呈现负相关趋势。中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接:  相似文献   

8.
背景:研究表明Ⅰ型胶原和Ⅲ型胶原都有利于骨髓间充质干细胞的黏附、增殖和分化。 目的:观察Ⅰ/Ⅲ型胶原膜联合自体骨髓间充质干细胞修复兔膝关节软骨缺损的可行性。 方法:取24只新西兰大白兔制作双膝股骨滑车直径3.8 mm、深2 mm关节软骨缺损模型,分为2组:实验组缺损区植入Ⅰ/Ⅲ型胶原膜-自体骨髓间充质干细胞复合物,对照组缺损区植入单纯Ⅰ/Ⅲ型胶原膜。 结果与结论:膝关节股骨标本组织学染色显示,实验组植入8周时为类透明软骨修复,12周时接近于正常软骨;对照组植入8周时以纤维样组织修复为主,12周时为纤维软骨修复。实验组植入后8,12周组织学评分均明显高于对照组(P < 0.001)。表明运用Ⅰ/Ⅲ型胶原膜-自体骨髓间充质干细胞复合物可修复关节软骨缺损。  相似文献   

9.
背景:大块软骨损伤目前临床上尚无方法治疗,干细胞技术出现后为解决这一难题提供了理论支持。采用新型的支架材料"壳聚糖-胶原蛋白"结合干细胞诱导分化移植给动物模型是一种较新的尝试。目的:观察壳聚糖-胶原凝胶复合骨髓间充质干细胞修复兔关节软骨缺损的组织学变化。方法:体外培养扩增兔骨髓间充质干细胞。采用软骨诱导分化培养基对P2代细胞进行成软骨诱导。同时制备"壳聚糖-胶原蛋白"支架和兔关节软骨缺损模型。缺损用含有骨髓间充质干细胞的壳聚糖-胶原凝胶填充,另一条关节用没有细胞的支架或不做处理。其中12个关节作为实验组(接受骨髓间充质干细胞+支架),8个关节作为空白对照组(不做处理),8个关节作为单纯支架组(未植入细胞)。造模后于2,4,8,16周进行组织学评分并处死动物行组织学染色。结果与结论:造模后16周移植的细胞一致分化为软骨细胞,大部分软骨缺损区被新生软骨修复,组织学评分实验组关节修复良好。提示应用骨髓间充质干细胞结合"壳聚糖-胶原蛋白"复合物可以修复关节软骨缺损。  相似文献   

10.
背景:研究显示,在众多的种子细胞中滑膜间充质干细胞对关节软骨损伤再生修复具有许多独特的优势。目的:对滑膜间充质干细胞的研究进展及其关节腔内注射治疗关节软骨损伤的应用进行综述。方法:第一作者通过计算机检索PubMed和CNKI数据库2004年1月至2014年12月的相关文献,检索关键词为“滑膜间充质干细胞、注射治疗、软骨修复;Synovial mesenchymal stem cells;Intra-articular injection;Cartilage repair”,纳入57篇文献进行分析。结果与结论:滑膜间充质干细胞分离培养方法简便,在软骨损伤修复方面具有很大的优势,通过将其注射于关节腔内治疗关节软骨损伤具有一定的可行性和安全性,作为一种潜在的治疗方式,有望给软骨损伤患者带来曙光,但仍然存在诸多问题,还需要进一步深入研究。中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程  相似文献   

11.
The occurrence of mast cells has been investigated in inflamed and control knee joints of rats suffering from antigen-induced arthritis, an animal model of rheumatoid arthritis in man. Rats were immunized with methylated bovine serum albumin (mBSA) followed by an intra-articular injection of mBSA (arthritis, right joints) or saline (control, left joints). Rats developed severe acute synovitis associated with cartilage erosion in the arthritic joints, whereas control joints did not show any noticeable changes. Mast cells were counted in synovial and adjacent tissues in cryostat sections of whole knee joints stained with Toluidine Blue O. The area of the synovium of each knee joint was determined using survey photomicrographs and a morphometer. Both total numbers of mast cells and frequency of mast cells in inflamed synovia were decreased after 1 day after induction of arthritis. The frequency of mast cells remained decreased up to 14 days after induction of arthritis. Morphological indications for degranulation of mast cells were never found in inflamed joints. It is concluded, therefore, that mast cells do not play a significant role in the inflammatory process during the early phase of arthritis.  相似文献   

12.
It is important to obtain high resolution images of joints for the study of disease, especially in rodent experimental models. We optimized (1)H magnetic resonance imaging three-dimensional sequences at 7 T, with lipid signal suppression, and T(1) and T(2) measurements for in-vivo experiments on rat joints, in order to assess the effectiveness of high-field MRI. The method was validated by applying it to the early diagnosis of arthritis. We studied the progress of rheumatoid arthritis in an arthritic rat model. We observed the rats' knees for 21 days after inducing arthritis. The images acquired over one hour had a high resolution of 1.75 x 10(-3) mm(3), (105 x 105 x 145 microm(3)) which allowed us to spot the early stages of joint degeneration, such as bone erosion, and to observe an apparent 'MRI' loss of cartilage thickness, attributed to dehydration of the cartilage tissue. The MR images obtained during the early stages of rheumatoid arthritis enabled us to study joint changes accurately before any histological signs of attack were visible.  相似文献   

13.
Septic arthritis is a serious condition, and, in adults, the knee is the most involved joint. Despite the availability of effective antibiotics, early drainage is essential to minimise the risk of permanent cartilage loss. This study was performed on 42 Holland Dutch rabbits. Two healthy rabbits (group O) were selected to characterise normal histology of the knee joint cartilage and synovium. Forty rabbits were divided randomly into four equal groups after inoculation by 0.5?ml solution of 105?CFU/ml of Staphylococcus aureus in the suprapatellar pouch of the right knee joint. After documentation of septic arthritis, no treatment was prescribed for rabbits in group A (diseased control group). Only antibiotic therapy and splinting were provided for group B. Antibiotic therapy in addition to multiple needle aspirations and splinting for group C and antibiotic therapy plus open arthrotomy drainage and splinting were prescribed for group D. Range of joint motion and pathologic findings of synovium and cartilage for destructive changes were compared in each group. Group D rabbits had less loss of cartilage (p?=?0.002) and synovial destruction (p?=?0.001) than group C after 3?weeks. Rabbits in group D had minimal loss of joint motion (<100), whereas group C and B had between 100–300 and 300–650 loss of motion, respectively. In conclusion, in aggressive types of septic arthritis, surgical drainage in addition to antibiotic therapy (as early as possible) is more reliable and safer than multiple needle aspirations and antibiotic therapy.  相似文献   

14.
背景:睾酮对骨关节炎的作用尚无一致的观点,其调节软骨代谢的作用鲜有文献报道。 目的:观察睾酮对膝骨关节炎雄兔关节软骨中胰岛素样生长因子1表达的影响。 方法:24只雄兔随机分成4组,采用改良Hulth法建立右膝骨关节炎模型;假去势组不切除睾丸,其余3组切除双侧睾丸。第8周末处死假去势组和去势8周组兔取材。第9周开始,激素组肌注生理剂量十一酸睾酮(6 mg/kg, 2周1次),去势16周组正常喂养,并于16周末处死并取材。 结果与结论:大体和组织学观察显示各组兔膝关节软骨的病变程度为假去势组优于去势8周组,激素组优于去势16周组。免疫组化染色显示胰岛素样生长因子1在所有兔膝关节软骨中均有表达,阳性细胞个数假去势组高于去势8周组(P < 0.05),激素组高于去势16周组(P < 0.05),去势8周组与去势16周组差异无显著性意义(P > 0.05)。说明睾酮可通过上调去势雄兔关节软骨中胰岛素样生长因子1的表达,延缓软骨退变。  相似文献   

15.
Fibroblast growth factor-2 (FGF-2) has the potential to regenerate damaged articular cartilage tissue due to its exerting anabolic effects on chondrocytes. However, FGF-2 is involved in pathogenesis of rheumatoid arthritis, where the joint is destructed. The study aims at clarifying the effects of FGF-2 on joints. When radiolabeled FGF-2 was injected into knee joints of C57Bl/10 mice, a transient binding was observed in the superficial and intermediate zones of the articular cartilage as well as in the synovium and perichondrium. An FGF-2 injection (5 microg) caused synovial hyperplasia adjacent to the articular cartilage on day 7, cartilage formation adjacent to the articular cartilage on day 14, and osteophyte on day 21. The intensity of safranin-O staining of the articular cartilage increased on day 14. These changes were dose-dependent. No destructive changes in the joints were observed. In a joint, transient exposure of FGF-2 caused proliferative changes, but not destructive changes.  相似文献   

16.
Effects of Resveratrol in Inflammatory Arthritis   总被引:4,自引:0,他引:4  
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17.
目的探讨Slit2表达在类风湿性关节炎大鼠滑膜中的作用及益赛普对类风湿性关节炎大鼠滑膜Slit2表达的影响。方法用弗氏完全佐剂皮下注射建立佐剂性关节炎模型,其中8只造模14 d后予益赛普治疗,取正常、模型及治疗组膝关节组织进行HE染色及免疫组化观察Slit2的表达。结果模型组病理学积分明显高于正常组,Slit2在佐剂性关节炎大鼠滑膜表达水平显著增加,且与时间相关,通过益赛普治疗后病理学积分减少,Slit2表达下调。结论 Slit2蛋白可能在大鼠佐剂性关节炎的发生发展中发挥着重要作用,益赛普可以下调Slit2蛋白的表达。  相似文献   

18.
背景:关节软骨与软骨下骨在骨关节炎病变进程中的相互作用机制目前尚未完全阐明。软骨下骨量改变在骨关节炎病理进程中亦发挥重要作用。 目的:分析2种手术方式及2种蛋白酶诱导建立兔膝关节骨关节炎动物模型的效果,以及软骨下骨量变化与关节软骨退变的相关性。 方法:32只新西兰大白兔随机分为4组:Hulth模型组、前交叉韧带切断模型组、Ⅱ型胶原蛋白酶组及木瓜蛋白酶组,每组8只,右膝关节造模,左膝关节作为自身对照。造模后0,4,8周行DXA扫描,8周行MRI扫描后处死实验动物,取双侧膝关节制作病理组织学切片,比较各组膝关节影像学表现、大体形态及病理变化,并采用Mankin评分进行定量分析。 结果与结论:造模后0,4,8周实验侧膝关节骨密度进行性降低,骨量降低程度Hulth模型组>前交叉韧带切断模型组>Ⅱ型胶原蛋白酶组>木瓜蛋白酶组。MRI显示实验侧股骨内外髁关节软骨厚度变薄,厚度Hulth模型组<前交叉韧带切断模型组<Ⅱ型胶原蛋白酶组<木瓜蛋白酶组。大体标本、组织切片观察及Mankin评分显示手术建模组骨关节炎程度较药物组重,Hulth模型组病变最重,木瓜蛋白酶组最轻。结果说明关节内手术及关节腔内注射蛋白酶均能建立骨关节炎动物模型;手术造模可复制出中晚期骨关节炎,药物诱导可产生骨关节炎早期改变。骨关节炎病变严重程度与软骨下骨骨密度呈负相关;关节软骨退变和软骨下骨改变相互关联,病变进行性发展。  相似文献   

19.
The goal of this study was to determine the efficacy of local IL-1Ra gene therapy by intra-articular plasmid injections on structural changes in the meniscectomy rabbit model of osteoarthritis. A partial meniscectomy of the right knee was performed on the rabbits through a medial parapatellar incision. The rabbits were then divided into four experimental groups. Group 1 received no treatment. Group 2 received three consecutive intra-articular injections at 24-hour intervals of 0.9% saline containing a lipid, gammaAP-DLRIE/DOPE, and a DNA plasmid, VR1012. Group 3 received three consecutive injections of saline containing 1000 microg of canine IL-1Ra plasmid and lipid. The injections were given starting 4 weeks post-surgery. Rabbits from Group 1 were killed 4 weeks post-surgery, and all other rabbits 8 weeks post-surgery. The severity of macroscopic and microscopic changes on cartilage on the medial and femoral condyles and tibial plateaus and synovium were graded separately. Specimens were also processed for immunohistochemical staining using a rabbit polyclonal antibody against canine IL-1Ra. The level of canine IL-1Ra in synovial fluid was determined using enzyme-linked immunosorbent assay. The presence of the DNA plasmid in the synovium was tested by polymerase chain reaction. A significant reduction in the width of osteophytes and size of macroscopic lesions (P < 0.04) was observed, and was dependent on the amount of IL-1Ra plasmid injected. A significant reduction was also noted in the severity of histologic cartilage lesions (P < 0.01) in the group that received the highest dosage (1000 microg) of IL-1Ra plasmid. IL-1Ra was detected in synovial fluid by enzyme-linked immunosorbent assay and by immunohistochemical staining in the synovium and cartilage of rabbits that received injections containing the IL-1Ra plasmid. Polymerase chain reaction analysis of synovial DNA revealed the presence of the cloned cDNA dog IL-1Ra up to 4 weeks after the first intra-articular injection. This study demonstrates that direct in vivo transfer of the IL-1Ra gene into osteoarthritis knee cells using intra-articular injections of a plasmid vector and lipids can significantly reduce the progression of experimental osteoarthritis. This avenue may therefore represent a promising future treatment for osteoarthritis.  相似文献   

20.
IntroductionMusculoskeletal findings in MPS can progress after enzyme replacement. Our aim was to examine synovial recesses, tendons, retinacula and pulleys using ultrasonography for structural and inflammatory changes.Material and methodsThe wrist, metacarpophalangeal (MCP), proximal and distal interphalangeal (PIP and DIP) joints, the finger flexor tendons and the knee including entheses of quadriceps and patella tendons were assessed clinically.Ultrasonography of the various synovial recesses of the wrist as well as the extensor retinaculum, carpal tunnel, MCP, PIP and DIP joints of the second finger, extensor and flexor tendons, A1-5 pulleys and the knee joint including relevant entheses followed. Significance of differences between patient values and available normative data were assessed using t-tests.ResultsUltrasonography showed significant abnormal intraarticular material in the wrist without a clear distribution to synovial recesses and without effusions. Doppler signals were found in a perisynovial distribution and not intrasynovial as expected in in inflammatory arthritis. Findings were similar in the knee but not the fingers. Flexor and extensor tendons were also mostly normal in their structure but significant thickening of retinaculae and the flexor tendon pulleys was seen (p<0.0001 compared to normal).ConclusionMPS I patients showed intraarticular deposition of abnormal material in the wrist and knee but not in the finger joints where significant thickening of retinaculae/pulleys controlling tendon position was dominant. No ultrasound findings of inflammatory pathology were demonstrated but rather a secondary reaction to abnormal deposition and direct damage of GAG.  相似文献   

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