Chinese Journal of Tissue Engineering Research ›› 2013, Vol. 17 ›› Issue (23): 4355-4362.doi: 10.3969/j.issn.2095-4344.2013.23.025
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Huang Shu-mei, Tian Jing
Online:
2013-06-04
Published:
2013-06-04
Contact:
Tian Jing, Professor, Associate chief physician, Master’s supervisor, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China tian_jing6723@yahoo.com.cn
About author:
Huang Shu-mei, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China Shirley12314@yahoo.com.cn
CLC Number:
Huang Shu-mei, Tian Jing. Intra-articular injection of mesenchymal stem cells for treatment of meniscusinjury[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(23): 4355-4362.
2.1 可分化为半月板纤维软骨细胞的不同来源间充质干细胞 间充质干细胞是成体干细胞,具有自我更新和维持未分化的能力,在一定内外环境因素的影响下可以激活并定向分化[8] ,成为成骨细胞,脂肪细胞,软骨细胞,滑膜细胞等多种组织细胞[9] 。间充质干细胞来源广泛, 骨髓间充质干细胞是最早报道可以从体内分离的间充质干细胞,同时也是目前使用最广的间充质干细胞[10] 。后续的研究发现脂肪组织[11] ,滑膜[12] ,骨骼肌[13] ,脐血[14] ,胎盘[15] ,骨膜[16] ,软骨等组织亦可以分离出间充质干细胞[17] ,且对机体的损伤更小。不同组织来源的间充质干细胞细胞数量,增殖及分化为纤维软骨细胞的能力都不同,这对于治疗过程中肝细胞的选择有非常重要的影响。Kisie等[18]发现骨髓,脂肪,骨骼肌和滑膜等组织中,每单位的骨膜组织分离的间充质干细胞数量最多,而四种间充质干细胞增殖活性没有明显的差别,这提示骨膜可成为间充质干细胞的良好细胞来源。Sakaguchi等[19-20]比较了人类骨髓间充质干细胞、骨膜间充质干细胞、滑膜间充质干细胞、骨骼肌间充质干细胞以及脂肪间充质干细胞等分化为软骨细胞的能力,发现滑膜间充质干细胞向软骨细胞分化的潜力最大,其次是骨髓间充质干细胞和骨膜间充质干细胞。然而,如何更好选择细胞来源广泛,体外培养方便,分化为软骨细胞能力强的间充质干细胞还需要更深入的研究和实验。 2.2 间充质干细胞注射入关节腔内后向损伤部位定向移动 关节腔内注射间充质干细胞治疗半月板损伤的一个难题是干细胞能否定位于缺损部位。大量研究表明,间充质干细胞直接注射到关节腔内后,可以迁移至损伤部位,直接参与组织修复,并且通过旁分泌途径诱导宿主的修补反应,替换损伤组织[21] 。Horie 等[22]实验中注射的滑膜间充质干细胞紧密结合在半月板损伤部位和滑膜上,间充质干细胞也可以有效地黏附在关节软骨和前交叉韧带的缺损处[23] 。实验证明在局部微环境的作用下,间充质干细胞可以迁移并移植到骨骼肌组织,尤其损伤部位,在黏附部分定向分化[24-25] 。目前介导注射细胞归巢的具体机制尚未完全明了,可能是由于损伤的半月板及关节囊的切口处会产生某些细胞因子或者趋化因子,如基质细胞衍生因子1、和单核细胞趋化蛋白1及转化生长因子β、白细胞介素α、血小板转化生长因子等可促进细胞的定向移动[26-27] 。 2.3 间充质干细胞定向分化为半月板纤维软骨细胞 体外培养过程对间充质干细胞分化的影响:间充质干细胞具有多向化分能,不同的培养条件可诱导向不同方向分化。体外培养过程中的很多因素会对细胞的增殖,分化和细胞的免疫原性产生影响,如:间充质干细胞分离提取的方法,培养皿表面性质,共培养细胞的选择,细胞密度,以及各种生长因子的使用等[28] 。在细胞培养基中加入不同的生长因子,可诱导间充质干细胞分化为不同的组织细胞。转化生长因子βs抑制间充质干细胞分化为脂肪细胞和成骨细胞,但可促进间充质干细胞分化为软骨细胞和心肌细胞[29] 。另有实验证明转化生长因子βs,骨形态发生蛋白,Sox9,纤维细胞因子以及血小板衍化生长因子等有效促进间充质干细胞分化为软骨细胞[30] 。透明质酸常用于治疗骨关节炎,其亦有利于提高间充质干细胞向软骨细胞分化的活性[31] 。已报道的实验研究中,只有由Centeno报道的一例实验在体外细胞培养过程中使用普通培养基,经皮下注射骨髓间充质干细胞来促进半月板的再生,大量实验研究结果表明在体外培养过程中加入生长因子明显促进间充质干细胞向软骨细胞的定向分化。可能原因为生长因子的作用可诱导间充质干细胞纤维软骨祖细胞转化,注射到关节腔后,间充质干细胞通过改变细胞形态和细胞骨架来控制细胞的定向分化[32] 。另外,有实验表明体外培养过程中流体静压力也可促进间充质干细胞分化为软骨细胞[33] 。 王志波[34]为探寻无血运区半月板损伤的治疗方式,以新西兰大白兔为实验动物,制作半月板损伤动物模型,并尝试使用以自体纤维蛋白胶为基质材料,以骨形态发生蛋白2为细胞因子,在无需传代扩增骨髓间充质干细胞的前提下,诱导间充质干细胞转化成纤维软骨细胞来修复半月板损伤。研究结果证实纤维蛋白胶是骨髓间充质干细胞及骨形态发生蛋白的理想载体,以纤维蛋白胶为载体的纤维蛋白胶+骨髓间充质干细胞+骨形态发生蛋白2复合物可以有效的促进和改善无血运区半月板损伤的修复,从而为临床治疗无血运区半月板损伤提供一种新的方法。尤微等[35]通过体外试验用特定细胞因子刺激诱导分离扩增后的兔骨髓间充质干细胞,使其分化为软骨细胞,为后续构建工程化半月板研究提供种子细胞,探讨兔骨髓间充质干细胞,重建半月板组织的可行性和有效性。结果显示已分离并经体外扩增的兔骨髓间充质干细胞在用碱性成纤维细胞生长因子和转化生长因子β1协同刺激后,细胞生长速度增快,免疫组织化学检测提示向软骨细胞系分化。说明碱性成纤维细胞生长因子、和转化生长因子β1能够加快骨髓间充质干细胞的体外增殖并促使使其向软骨细胞系分化,为构建工程化半月板提供了可靠的自体来源种子细胞。 关节腔内局部微环境对间充质干细胞分化的影响:目前大量实验结果表明间充质干细胞可分泌多种免疫活性调节因子,如一氧化氮(NO)、加双氧酶(IDO)等[36],和促再生活性因子[37] ,间充质干细胞移植到关节腔后,通过细胞与细胞之间的直接作用或者分泌多种活性因子,调节局部微环境,从而激活内源性再生细胞促进局部组织的修复[38] 。Horie等[22]证实半月板损伤后,周围的关节软骨,滑膜组织,残留半月板,以及关节滑液,和机械压力都会影响微环境。这种微环境的变化本身可提供足够的信号诱导和维持间充质干细胞向半月板细胞定向分化。相似的,在不同的微环境影响下,间充质干细胞可以分化为不同的组织细胞,Koga等[39]发现未分化的间充质干细胞植入缺损的关节软骨中可定向分化为关节软骨细胞。Birminghan等[40]发现间充质干细胞体外培养过程加入成骨细胞或者骨细胞共培养时,成骨细胞或者骨细胞产生的生物信号可以有效的诱导间充质干细胞成骨分化,且骨细胞共培养的结果更明显。但是目前对于微环境变化可以诱导间充质干细胞定向分化的具体机制尚未十分明了,研究发现细胞内染色体端粒的长度和端粒酶的活性对细胞的分化有一定的影响[41] 。 2.4 关节腔内注射干细胞促进半月板损伤后再生 间充质干细胞在半月板缺损处再生:Horas等[42]于2003年首次将组织工程及细胞疗法治疗关节和骨骼疾病应用于临床。目前,间充质干细胞,尤其骨髓间充质干细胞的研究越来越多[43] ,强大的研究热潮源于Murhpy于2003年发表的一篇关于在羊关节腔内注射骨髓间充质干细胞的研究报道。Murphy等[44]在摘除半月板的羊关节腔内注射间充质干细胞,6周和12周后观察,可见间充质干细胞治疗组与单纯透明质酸治疗组或者生理盐对照组相比,关节软骨损伤修复和半月板损伤修复结果明显。AL Fageh等[45]在摘除前交叉韧带和内侧半月板的动物模型上观察到间充质干细胞治疗组的手术切口部位见半月板样组织形成,显微镜下显示为不完全成熟半月板纤维软骨细胞。可以推测治疗时间足够长时,该组织可形成正常半月板。Horie等[22,46]在大鼠关节内注射滑膜间充质干细胞治疗半月板大面积缺损。结果显示滑膜干细胞黏附在缺损部位,直接分化为半月板纤维软骨细胞,促进了半月板再生,同时滑膜干细胞未迁移至其他组织或器官[47] 。王志波等[48]在膝关节半月板损伤区注入纤维蛋白胶+骨髓间充质干细胞+骨形态发生蛋白混合物后,缺损区修复组织与周围组织融合良好,三者可有效的促进和改善半月板无血运区损伤的修复。Agung等[21]在前交叉韧带,内侧半月板和股骨髁关节软骨损伤的SD大鼠,注射低浓度的干细胞只能迁移至交叉韧带的损伤部位,较高浓度的干细胞可迁移至交叉韧带,半月板和关节软骨的损伤部位,并且可见损伤部位组织明显再生。以上实验研究都提示膝关节创伤性损伤后行关节腔内注射间充质干细胞可有助于半月板损伤的修复,长远而言将有利于延缓骨关节炎的病程进展或者降低骨关节炎的发生率[49] 。 间充质干细胞促进半月板缝合后的修复:关节镜可用于半月板损伤的治疗,半月板边缘撕裂可行缝合修复,通常行半月板部分切除,保留未损伤的部分。对早期怀疑半月板损伤者可行急诊关节镜检查,早期处理半月板损伤,缩短疗程,提高治疗效果,减少损伤性关节炎的发生。半月板的损伤,尤其是无血管区的损伤其缝合治疗效果不理想[50] 。在家兔或其他实验动物中,半月板缝合不能促进修复过程[51] ,人类中此类撕裂伤缝合后的治愈率低于20%-30%。Ruiz-Ibán等[52]的实验结果表明半月板损伤缝合后加入脂肪间充质干细胞提高了治愈率。半月板全层纵行损伤的长度对最后半月板愈合的影响不明显。但是损伤后延迟缝合,间充质干细胞促进愈合的效果不明显。该试验提示间充质干细胞促进急性半月板损伤的修复的效果明显,但对于慢性半月板损伤的修复效果不明显。 间充质干细胞在临床中应用:目前间充质干细胞治疗半月板缺损的数据主要来源于动物实验,临床上间充质干细胞治疗半月板损伤仍处于临床实验阶段[53] ,间充质干细胞 治疗半月板急性损伤的数据尚缺乏。Centeno等[54]在一位骨关节炎患者关节内注射透明质酸后注射间充质干细胞。注射间充质干细胞后一周及两周时再注射血小板溶解产物及地塞米松。实验前后MRI结果比较显示半月板的体积增大,患者主述疼痛减轻,膝关节活动范围增大。该试验证明了关节腔内注射间充质干细胞的治疗方法可能也使用于人类,然而间充质干细胞治疗人半月板损伤仍处于早期临床试验阶段,确切的治疗效果需要大规模随机临床实验的开展和更深入的研究。 2.5 半月板再生的细胞组织工程技术 组织工程技术是生长因子治疗、基因治疗、细胞治疗、基质支架研究等的综合应用,利用功能细胞及基质支架培育出工程组织重建或替代损伤的半月板。主要包括功能细胞选择、基质支架研究以及生物反应器的研究。半月板纤维软骨细胞、间充质干细胞是目前研究最多的半月板组织再生的功能细胞[55] 。 干细胞移植法是目前医学领域比较先进和前沿的治疗方法,是世界先进的医疗水平的重要组成部分,该疗法可以从根源上改善骨科疾病患者的血液循环功能与肌肉及组织营养供给、调节免疫系统和内分泌系统功能,修复脊髓损伤、骨纤维病变、促进患者微循环改善,恢复机体正常功能的同时,提高患者生活质量,有效避免由骨科疾病引发的眼、肺、肌肉、骨骼病 变的产生,是骨科疾病提供了有效的治疗方式[56] 。 干细胞定向诱导及转化生长因子β1基因修饰术,通过调节多种细胞的生长和分化,诱导骨髓间充质干细胞向软骨细胞方向分化,组织工程技术治疗半月板损伤必将在临床领域获得更大进展。朱现玮等[57] ,观察丝素蛋白/羟基磷灰石复合骨髓间充质干细胞修复兔半月板无血运区软骨损伤效果,实验结果证明,复合材料组大体观察损伤被修复组织填充,8-12周效果逐渐改善,与正常半月板组织相似,优于其他两组;组织学检查显示8周时出现软骨囊和排列紊乱的胶原纤维,12周时完全修复了半月板损伤区,表现为纤维软骨样组织愈合;单纯材料组部分修复了半月板损伤区,呈瘢痕愈合,对照组未见软骨修复,MRI检查显示复合材料组修复效果较好;说明丝素蛋白/羟基磷灰石复合骨髓间充质干细胞可有效地修复半月板无血运区缺损,丝素蛋白/羟基磷灰石材料作为半月板软骨组织工程支架材料的良好生物相容性。徐青镭等[58]将已分离并经体外传代培养扩增的兔骨髓间充质干细胞在用磁性成纤维细胞生长因子和转化生长因子β1协同刺激后,用反转录-聚合酶链式反应的方法从分子水平寻找进入软髓细胞分化谱系的证据。结果显示已分离并经体外扩增的兔髓髓骨髓间充质干细胞在用成纤维细胞生长因子和转化生长因子β1协同刺激后,用RT-CPR的方法探明有pC-I的编码基因表达,证明其已经进入软骨细胞分化谱系,说明成纤维细胞生长因子和转化生长因子β1能够刺激间充质干细胞的体外增殖并且使进入软髓细胞分化谱系,为半月板组织工程重建提供了可靠的自体来源种子细胞。 李杰等[59]总结了骨髓基质干细胞在治疗和修复膝关节半月板损伤方面具有独到的优势,其中包括其损伤面较小,方便易行,没有后遗症,并克服了切除半月板引起的形态和生物功能的改变,避免了因异体材料移植引起的膝载荷传导紊乱和晚期骨性关节炎发病的可能,与保留半月板修复其功能的临床治疗理念较为接近,并成为当前和今后治疗与修复膝关节半月板损伤的新思路。而在其修复治疗的过程中,其关键问题在于一方面如何获得大量纯化的骨髓基质干细胞并在体外定向诱导为半月板软骨表型的细胞,另一方面是诱导分化的确切机制研究。"
[1]张经纬,冯建翔,徐荣明,等. 慢病毒介导碱性成纤维细胞生长因子基因转染促进半月板纤维软骨细胞的增殖与基质合成[J]. 中国组织工程研究与临床康复,2007,11(41):8267-8270.[2]朱文辉,王予彬. 膝关节半月板损伤后愈合的细胞分子生物学研究进展[J].中国微创外科杂志, 2008,8(8):752-754.[3]Andersson-Molina H, Karlsson H, Rockborn P. Arthroscopic partial and total meniscectomy: A long-term follow-up study with matched controls. Arthroscopy. 2002;18(2):183-189.[4]Cui X, Hasegawa A, Lotz M, et al .Structured Three-Dimensional Co-Culture of Mesenchymal Stem Cells With Meniscus Cells Promotes Meniscal Phenotype Without Hypertrophy.Biotechnol Bioeng. 2012;109:2369-2380.[5]Somoza RA ,Rubio FJ. Cell therapy using induced pluripotent stem cells or somatic stem cells:this is the question.Curr Stem Cell Res Ther. 2012;7(3):191-196.[6]吴鹏飞,邓亮,谷文光,等.半月板损伤与修复研究进展[J].中国矫形外科杂志,2011,19(20):1706-1709.[7]张海宁,冷萍,王英振,等.骨髓基质干细胞复合藻酸钙凝胶修复全层半月板无血运区缺损[J].中华外科杂志,2010,48(17):1309- 1312.[8]Prosecka E, Buzgo M, Rampichova M, et al. Thin-layer hydroxyapatite deposition on a nanofiber surface stimulates mesenchymal stem cell proliferation and their differentiation into osteoblasts. Biomed Biotechnol. 2012; 2012:428-503.[9]Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315-317.[10]Kassem M, Abdallah BM. Human bone-marrow-derived mesenchymal stem cells: biological characteristics and potential role in therapy of degenerative diseases. Cell Tissue Res. 2008;331(1):157-163.[11]Minteer D, Marra KG, Rubin JP. Adipose-Derived Mesenchymal Stem Cells: Biology and Potential Applications. Adv Biochem Eng Biotechnol. 2012 Jul 24.[12]Zhao W, Xing G, Yu S. Application of synovium-derived mesenchymal stem cells in tissue engineering. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi.2011;25(12):1504-1507.[13]Jackson W M, Lozito T P, Djouad F, et al. Differentiation and regeneration potential of mesenchymal progenitor cells derived from traumatized muscle tissue.Cell Mol Med.2011; 15(11):2377-2388.[14]Moretti P, Hatlapatka T, Marten D, et al. Mesenchymal stromal cells derived from human umbilical cord tissues: primitive cells with potential for clinical and tissue engineering applications. Adv Biochem Eng Biotechnol. 2010;123:29-54.[15]Bacenkova D, Rosocha J, Tothova T, et al. Isolation and basic characterization of human term amnion and chorion mesenchymal stromal cells. Cytotherapy.2011;13(9):1047- 1056.[16]Ringe J, Leinhase I, Stich S, et al. Human mastoid periosteum-derived stem cells: promising candidates for skeletal tissue engineering. Tissue Eng Regen Med. 2008; 2(2-3):136-146.[17]Mohal JS, Tailor HD, Khan WS. Sources of adult mesenchymal stem cells and their applicability for musculoskeletal applications. Curr Stem Cell Res Ther. 2012;7(2):103-109.[18]Kisiel AH, Mcduffee LA, Masaoud E, et al. Isolation, characterization, and in vitro proliferation of canine mesenchymal stem cells derived from bone marrow, adipose tissue, muscle, and periosteum. Am J Vet Res. 2012;73(8): 1305-1317.[19]Sakaguchi Y, Sekiya I, Yagishita K, et al. Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. Arthritis Rheum. 2005;52(8):2521-2529.[20]Li Q, Tang J, Wang R, et al. Comparing the chondrogenic potential in vivo of autogeneic mesenchymal stem cells derived from different tissues. Artif Cells Blood Substit Immobil Biotechnol.2011;39(1):31-38.[21]Agung M, Ochi M, Yanada S, et al. Mobilization of bone marrow-derived mesenchymal stem cells into the injured tissues after intraarticular injection and their contribution to tissue regeneration. Knee Surg Sports Traumatol Arthrosc. 2006;14(12):1307-1314.[22]Horie M, Sekiya I, Muneta T, et al. Intra-articular Injected synovial stem cells differentiate into meniscal cells directly and promote meniscal regeneration without mobilization to distant organs in rat massive meniscal defect. Stem Cells. 2009;27(4):878-887.[23]Koga H, Shimaya M, Muneta T, et al. Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect. Arthritis Res Ther. 2008;10(4):R84.[24]Papadopoulou A, Yiangou M, Athanasiou E, et al. Mesenchymal stem cells are conditionally therapeutic in preclinical models of rheumatoid arthritis. Ann Rheum Dis. 2012;71(10):1733-1740.[25]Chen FH, Tuan RS. Mesenchymal stem cells in arthritic diseases. Arthritis Res Ther. 2008;10(5):223.[26]Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. Cell Biochem. 2006;98(5):1076-1084.[27]Miller MD. Re: Expression of cytokines after meniscal rasping to promote meniscal healing. Arthroscopy. 2002; 18(5):563.[28]Sotiropoulou PA, Perez SA, Salagianni M, et al. Characterization of the optimal culture conditions for clinical scale production of human mesenchymal stem cells. Stem Cells. 2006;24(2):462-471. [29]Watabe T, Miyazono K. Roles of TGF-beta family signaling in stem cell renewal and differentiation. Cell Res.2009;19(1): 103-115. [30]Zhang Y, Khan D, Delling J, et al. Mechanisms underlying the osteo- and adipo-differentiation of human mesenchymal stem cells. Scientific World Journal. 2012;2012:793-823.[31]Kavalkovich KW, Boynton RE, Murphy JM, et al. Chondrogenic differentiation of human mesenchymal stem cells within an alginate layer culture system. In Vitro Cell Dev Biol Anim. 2002;38(8):457-466.[32]Park JS, Chu JS, Tsou AD, et al. The effect of matrix stiffness on the differentiation of mesenchymal stem cells in response to TGF-β. Biomaterials. 2011;32(16):3921- 3930.[33]Safshekan F, Tafazzoli-Shadpour M, Shokrgozar MA, et al. Intermittent Hydrostatic Pressure Enhances Growth Factor-Induced Chondroinduction of Human Adipose-Derived Mesenchymal Stem Cells. Artif Organs. 2012 Aug 10.[34]王志波.BMP-2诱导MSCs修复无血运区半月板损伤的实验研究[J].青岛大学,2012.[35]尤微,熊建义,曹清丽,等.细胞因子诱导骨髓间充质干细胞构建工程化半月板种子细胞[J].深圳中西医结合杂志, 2010,4:197-200.[36]赵玉鑫,王洪,杨述华,等. 半月板纤维软骨细胞与小肠黏膜下层的组织相容性[J].中国组织工程研究与临床康复,2007,11(2): 206-208.[37]Shi Y, Hu G, Su J, et al. Mesenchymal stem cells: a new strategy for immunosuppression and tissue repair. Cell Res. 2010;20(5):510-518. [38]Koelling S, Miosge N. Stem cell therapy for cartilage regeneration in osteoarthritis. Expert Opin Biol Ther. 2009;9(11):1399-1405. [39]Koga H, Muneta T, Ju YJ, et al. Synovial stem cells are regionally specified according to local microenvironments after implantation for cartilage regeneration. Stem Cells. 2007; 25(3):689-696.[40]Birmingham E, Niebur GL, McHugh PE, et al. Osteogenic differentiation of mesenchymal stem cells is regulated by osteocyte and osteoblast cells in a simplified bone niche. Eur Cell Mater. 2012;23:13-27.[41]Mirsaidi A, Kleinhans KN, Rimann M, et al. Telomere length, telomerase activity and osteogenic differentiation are maintained in adipose-derived stromal cells from senile osteoporotic SAMP6 mice. J Tissue Eng Regen Med. 2012;6(5):378-390.[42]Horas U, Pelinkovic D, Herr G, et al. Autologous chondrocyte implantation and osteochondral cylinder transplantation in cartilage repair of the knee joint. A prospective, comparative trial. J Bone Joint Surg Am. 2003;85-A(2):185-192.[43]Madry H, Cucchiarini M. Clinical potential and challenges of using genetically modified cells for articular cartilage repair. Croat Med J. 2011;52(3):245-261.[44]Murphy JM, Fink DJ, Hunziker EB, et al. Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum. 2003; 48(12): 3464-3474.[45]Al Faqeh H, Nor Hamdan BM, Chen HC, et al. The potential of intra-articular injection of chondrogenic-induced bone marrow stem cells to retard the progression of osteoarthritis in a sheep model. Exp Gerontol. 2012;47(6):458-464.[46]Horie M, Driscoll MD, Sampson HW, et al. Implantation of allogenic synovial stem cells promotes meniscal regeneration in a rabbit meniscal defect model. J Bone Joint Surg Am. 2012; 94(8):701-712.[47]孙延山,卢斌,姜鑫,等.血管内皮细胞生长因子与半月板白区修复中新生血管的长入[J].中国组织工程研究与临床康复, 2011, 15(15):2669-2671.[48]王志波,王德春. BMP-2诱导MSCs修复无血运区半月板损伤的实验研究[J].中国社区医师:医学专业,2011,31:3-4.[49]Qi Y, Feng G, Yan W. Mesenchymal stem cell-based treatment for cartilage defects in osteoarthritis. Mol Biol Rep. 2012;39(5):5683-5689.[50]Gallacher PD, Gilbert RE, Kanes G, et al. White on white meniscal tears to fix or not to fix?. Knee. 2010;17(4):270-273.[51]Becker R, Pufe T, Kulow S, et al. Expression of vascular endothelial growth factor during healing of the meniscus in a rabbit model. Bone Joint Surg Br. 2004;86(7):1082-1087.[52]Ruiz-Ibán MÁ, Díaz-Heredia J, García-Gómez I, et al. The effect of the addition of adipose-derived mesenchymal stem cells to a meniscal repair in the avascular zone: an experimental study in rabbits. Arthroscopy. 2011;27(12): 1688-1696.[53]Steinert AF, Ghivizzani SC, Rethwilm A, et al. Major biological obstacles for persistent cell-based regeneration of articular cartilage. Arthritis Res Ther. 2007;9(3):213.[54]Centeno CJ, Busse D, Kisiday J, et al. Regeneration of meniscus cartilage in a knee treated with percutaneously implanted autologous mesenchymal stem cells. Med Hypotheses.2008;71(6):900-908.[55]吴伟,陈世益. 半月板损伤修复的研究进展[J].中国运动医学杂志,2004,23(6):657-659. [56]裴彩利.半月板运动损伤的组织工程修复[J].中国组织工程研究与临床康复,2011,15(46):8718-8721.[57]朱现玮,徐卫袁,张兴祥,等.多孔型丝素蛋白/羟基磷灰石复合骨髓间充质干细胞修复兔半月板无血运区软骨损伤[J].中国组织工程研究, 2012,16(29):5375-5378.[58]徐青镭,万年宇,吴海山,等.兔骨髓干细胞向软骨细胞分化用于半月板组织工程重建[J].中国临床康复,2003,7(6):912-913.[59]李杰,刘富顺.膝关节半月板损伤与骨髓基质干细胞[J].中国组织工程研究,2012,16(14):2617-2620.[60]Welch JA,Montgomery RD,Lenz SD,et al.Evaluation of small-intestinal submucosa implants for repair of meniscal defects in dogs.Am J Vet Res 2002;63(3):427-431.[61]Hong JH, Park JI, Kim KH, et al. Repair of the Complete Radial Tear of the Anterior Horn of the Medial Meniscus in Rabbits: A Comparison between Simple Pullout Repair and Pullout Repair with Human Bone Marrow Stem Cell Implantation. Knee Surg Relat Res. 2011;23(3):164-170.[62]Barthel C, Yeremenko N, Jacobs R, et al. Nerve growth factor and receptor expression in rheumatoid arthritis and spondyloarthritis. Arthritis Res Ther. 2009;11(3):R82. |
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