Chinese Journal of Tissue Engineering Research ›› 2020, Vol. 24 ›› Issue (7): 1117-1122.doi: 10.3969/j.issn.2095-4344.1863
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Application and prospect of bone marrow mesenchymal stem cells in the
treatment of early femoral head necrosis
Wang Tiantian1, Wang Jianzhong2
Received:
2019-05-05
Revised:
2019-05-21
Accepted:
2019-07-05
Online:
2020-03-08
Published:
2020-01-20
Contact:
Wang Jianzhong, Professor, Master’s supervisor, Department of Traumatic Orthopedics, Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010030, Inner Mongolia Autonomous Region, China
About author:
Wang Tiantian, Master candidate, Inner Mongolia Medical University, Hohhot 010030, Inner Mongolia Autonomous Region, China
CLC Number:
Wang Tiantian, Wang Jianzhong.
Application and prospect of bone marrow mesenchymal stem cells in the
treatment of early femoral head necrosis
2.1 股骨头坏死的病因及机制 根据病因,可分为创伤性股骨头坏死和非创伤性股骨头坏死,创伤性股骨头坏死主要包括股骨颈骨折、髋关节脱位等,非创伤性股骨头坏死主要包括长期大剂量使用糖皮质激素、过度饮酒、器官移植、减压病、链状细胞贫血、自身免疫性疾病等[2-3]。长期或大剂量运用皮质激素已成为非创伤股骨头坏死的首位发病因素[4]。大量运用激素对平滑肌细胞产生毒性作用,促进蛋白质分解,使胶原蛋白和弹性蛋白的合成不足,以至于血管壁的支持力减弱而破裂。激素还可分解脂肪,增加血中游离脂肪酸,骨内小血管发生炎症以及内皮细胞增生。在这些致病因素作用下,最终直接或间接造成股骨头供血不足或中断,使骨的活性成分死亡,包括骨细胞、骨髓细胞、造血细胞及脂肪细胞等,破骨细胞成活时间延长,骨细胞凋亡后生成的骨基质会被分解吸收,导致骨丢失及骨质稀少疏松,最终发生股骨头缺血坏死。各种创伤和非创伤因素也会破坏股骨头循环,导致骨髓和骨细胞死亡[5]。目前有多种学说,包括血管内凝血学说、脂肪代谢紊乱以及骨内高压学说、动脉血管炎学说等。随着细胞生物学、分子生物学的不断深入研究,认为细胞凋亡、骨髓基质干细胞脂肪分化、基因多态性与股骨头坏死发生发展密切相关。 2.2 股骨头坏死的诊断及分期 股骨头坏死早期诊断和治疗是减缓股骨头关节面塌陷以及减少全髋关节置换术的重中之重。目前骨坏死的诊断依赖于髋关节的正位和蛙腿侧位平片,然后是磁共振成像。一般而言,X射线检查发现的第一个影像学变化是股骨头囊性和硬化性变化。普通X射线片通常不足以进行早期诊断,早期股骨头缺血坏死患者的骨密度以及股骨结构没有较大的差别,但是骨髓细胞已经出现由于缺血导致死亡的情况。CT虽具有较高的骨密度分辨率、空间分辨率,能够清晰观察到骨小梁、骨小囊病变,如果只存在骨髓肿胀情况那它的诊断率就会相当低,而且患者的股骨头出现骨化或者骨吸收后才能检测出来。MRI对股骨头缺血性坏死进行检查过程中,可以对软组织产生水平较高的分辨率,对骨髓水肿、坏死、肉芽浸润等进行清晰显示,病灶大小的量化有助于预测股骨头塌陷,因此MRI被认为是最准确的诊断标准[6]。MRI对股骨头坏死的诊断敏感性为90%-100%,特异性为100%,对早期发现无症状股骨头坏死也有意义[7]。有许多分类系统描述了股骨头坏死的临床和放射学严重程度和进展,Ficat和Arlet分期系统是最常用的分类系统,但没有考虑坏死范围。美国骨循环研究协会(ARCO)的分类系统整合了Ficat和Arlet系统以及Steinberg分类的特征,常应用于临床。 早期诊断和治疗是保髋成功的关键。髓芯减压是一种广泛应用于早期股骨头坏死的方法,其目的是减轻股骨头内高压,改善股骨头内的血液循环,并为坏死区域修复及血管化创造条件,但其临床效果仍存在争议[8]。一旦股骨头塌陷(> 2 mm)或出现继发性退变,髋关节保留手术就变得无效,全髋关节置换术仍然是唯一更好的可靠选择。全髋关节置换也有其缺点,包括植入物的使用寿命有限以及手术并发症(如感染、脱位等),接受全髋关节置换的年轻患者在他们的一生中至少需要一次翻修[9]。 2.3 骨髓间充质干细胞治疗的理论依据 干细胞是机体各个组织和器官的最初来源,具有很强的增殖及分化能力,随着医学技术的快速发展,其在组织工程、细胞移植以及再生医学方面发挥重要作用。骨组织工程是组织工程领域中发展最为迅速的学科。骨髓间充质干细胞是来源于中胚层的具有多向分化潜能的干细胞,单个细胞呈纺锤状或者梭形,整体呈菊花状或同心圆状排列。20世纪60年代由德国学者FRIEDENSTEIN首次发现,主要存在于全身结缔组织和器官间质中,其中以骨髓组织中含量最为丰富[10]。在一定的诱导条件下可分化成中胚层细胞如成骨细胞、脂肪细胞、软骨细胞、平滑肌细胞等,同时还可以分化成外胚层细胞如星形胶质细胞、神经元、血管内皮细胞[11-12]。骨髓间充质干细胞是骨组织工程中广泛研究的骨祖细胞之一,其具有多方向分化潜能。骨髓间充质干细胞分化能力取决于细胞所处的局部环境以及与之接触的各种细胞因子和生长因子[13]。实验证明,骨髓间充质干细胞可在地塞米松、抗坏血酸以及β-甘油磷酸钠的诱导下形成钙化结节,表达碱性磷酸酶,向成骨方向转化[14]。细胞因子包括胰岛素样生长因子、成纤维细胞生长因子、转化生长因子β、血小板源生长因子以及骨形态发生蛋白等在骨髓间充质干细胞诱导成骨过程中与骨形成、骨愈合、骨重建有着密切关系[15]。骨髓间充质干细胞能分化为成骨细胞来促进骨小梁的恢复。此外,骨髓间充质干细胞分泌大量血管生成因子、转化生长因子β、基质细胞衍生因子1等。血管内皮生长因子在骨形成和修复过程中必不可少。它是由多种细胞分泌的糖蛋白,是特异性促进血管内皮细胞增殖的最有力的血管生成因子。骨形成蛋白是一类能够促进软骨细胞增殖与分化、促进毛细血管内皮细胞增殖的细胞生长因子,对血液循环重建具有重要作用。骨髓间充质干细胞的生理作用不仅在于其可以分化为相应的成熟细胞,而且可以保持一个合适的微环境[16-17]。另外,骨髓间充质干细胞很容易从骨髓中分离,并且骨髓间充质干细胞移植不会诱导任何免疫排斥。 2.4 骨髓间充质干细胞与股骨头坏死 研究表明,骨髓间充质干细胞可能影响股骨头坏死的发生,已经发现股骨头坏死患者中骨髓间充质干细胞的数量和活性降低,并且成骨分化能力降低[18]。GANGJI等[19]报道股骨头坏死患者股骨近端成骨细胞复制能力下降。在坏死区域成骨细胞和骨细胞凋亡率增加[20],这一发现表明新鲜骨髓间充质干细胞移植到坏死病变可能是一种有效的治疗方法。目前,运用骨髓间充质干细胞治疗股骨头坏死的方法主要有髓芯减压联合骨髓间充质干细胞注射、介入联合骨髓间充质干细胞、基因转染骨髓间充质干细胞移植、骨髓间充质干细胞的组织工程技术等,见表1。 "
2.4.1 髓芯减压联合骨髓间充质干细胞注射治疗 研究表明,股骨头坏死与骨髓内压力升高有关,髓腔内脂肪细胞肥大和脂肪细胞聚集导致骨内血液回流受阻和停滞,灌注量下降,最终骨细胞坏死[21]。在髓芯减压后将自体骨髓间充质干细胞植入股骨头病损中心是股骨头坏死的治疗方法之一。坏死的股骨头经髓芯钻孔后,将通过离心或其他方式得到的骨髓间充质干细胞注入坏死和病变部位,达到修复、重建或永久替代坏死股骨头的目的。通常提纯的骨髓间充质干细胞在植入股骨头髓芯前需加入载体混合,制成骨髓间充质干细胞/生物纤维胶原复合物植入股骨头髓芯病灶部位。与单纯的髓芯减压相比,髓芯减压与再生技术结合在一定程度上提高了存活率。PAPAKOSTIDIS等[22]、王谦等[23]Meta分析表明,与髓芯减压比较,髓芯减压联合自体骨髓干细胞可降低患者髋关节疼痛、改善髋关节Harris评分、减少股骨头坏死影像学进展率,降低髋关节置换手术需求。SEN等[24]用51髋(ARCOⅠ、Ⅱ期)进行临床试验,单纯髓芯减压组25髋,髓芯减压后自体骨髓单个核细胞移植组26髋,经过24个月随访,通过两组的髋关节Harris评分、影像学检查和髋关节Kaplan-Meier生存分析,发现髓芯减压联合骨髓间充质干细胞移植较单纯髓芯减压效果好。最近的一些研究显示,将自体骨髓间充质干细胞植入到经髓芯减压后的股骨头病损中心,治疗股骨头崩塌前的早期阶段股骨头坏死,股骨头存活率显著提高,人工髋关节置换术的需求也有所下降。Ⅲ期和Ⅳ期股骨头坏死患者可能容易出现不良结局。股骨头坏死分期可能影响干细胞治疗的疗效。HERNIGOU等[25]报道了116例接受髓芯减压和自体骨髓移植治疗的股骨头坏死患者189髋(其中ARCOⅠ、Ⅱ期145髋,ARCOⅢ、Ⅳ期44髋)的前瞻性研究结果,将自体骨髓离心后得到单核细胞经减压孔道注入坏死股骨头,经过5-10年随访,早期股骨头坏死的145髋有9髋需要接受全髋关节置换,晚期股骨头坏死的44髋有25髋需要进行全髋关节置换。GANGJI等[26]研究也证实髓芯减压联合骨髓间充质干细胞治疗早期股骨头坏死的有效性,但是对于晚期股骨头坏死的治疗效果不理想。 2.4.2 介入联合骨髓间充质干细胞治疗 治疗早期股骨头坏死的关键是恢复股骨头的血液供应,股骨头骨髓的微血管结构为珊瑚形,其特征为毛细血管微动脉与微静脉部分膨大、迁曲、互相缠绕,股骨头软骨血管与软骨下平面呈垂直走行并扩展为血窦,然后转折180°中止于骨静脉,此处终末动脉与迂曲拱形的终末毛细血管相连。由于其具有特殊的解剖结构,使高黏滞状态的血液容易滞留在此,引发局部缺血。介入治疗旨在解决股骨头坏死的微循环障碍问题,将干细胞、溶栓剂、外周血管扩张药物和活血化瘀中药等大剂量注入股骨头局部供血动脉内,疏通股骨头的供血动脉及侧支循环,改善微循环,促进死骨吸收及新骨形成,该方法对Ⅰ、Ⅱ期患者有较好的中远期疗效,Ⅲ期患者在短期内可缓解疼痛症状,但中远期疗效差。有动物实验证实,介入联合骨髓间充质干细胞可以使股骨头血管扩张,动脉管径平均增加20%,管腔横面积平均增加40%,改善了病变局部股骨头微循环,恢复股骨头的血液供应。介入治疗后血管造影显示,股骨头供血区动脉增多和增粗,血流速度加快,治疗后的血供增加20%-110%[27]。季卫峰等[28]通过兔股骨头坏死动物模型进行介入联合骨髓间充质干细胞治疗,经2周后出现了间充质细胞的增生,在周围骨小梁表面有明显的新骨形成,并伴有大量血管增生,空骨陷窝减少,成骨细胞增多,促进兔股骨头的再血管化和再骨化进程。童培建等[29]随访62例78髋经介入联合骨髓间充质干细胞治疗非创伤性股骨头坏死患者,术后随访9-13年,Harris评分较术前有明显提高,疼痛及功能改善明显。MAO等[30]研究也表明介入联合骨髓间充质干细胞治疗股骨头坏死是一种安全有效的方法,为治疗早期股骨头坏死提供了新的思路。 2.4.3 基因转染骨髓间充质干细胞移植治疗 基因转染骨髓间充质干细胞移植是修复股骨头坏死的有效方法之一。MA等[31]研究表明,与单纯骨髓间充质干细胞移植相比,转染了骨形态发生蛋白/血管内皮生长因子的骨髓间充质干细胞,对股骨头坏死的疗效更确切。白志刚等[32]构建兔缺血性股骨头坏死模型,将转染人血管内皮生长因子165基因的骨髓间充质干细胞植入到坏死股骨头处,持续、长效表达血管内皮生长因子,从而促进血管再生及新骨形成,最终完成死骨的爬行替代作用,使坏死的股骨头得以修复。DING等[33]制备早期激素诱导的股骨头坏死兔模型,证明缺氧诱导因子1α转染增强骨髓间充质干细胞促进成骨和血管生成的能力。HANG等[34]使用血管内皮生长因子165基因转染的骨髓间充质干细胞治疗狗股骨头坏死,发现效果优于未转染基因的骨髓间充质干细胞治疗组和单纯髓芯减压组,在骨小梁的骨板上可见新生成的毛细血管,并且骨髓富含造血组织。Bcl-2被认为是抑制细胞凋亡这一过程中最重要的基因。它的主要生理功能是增加细胞的存活时间,而不影响细胞周期和分化能力。张立岩等[35]用Bcl-2基因转染骨髓间充质干细胞结合髓芯减压法治疗兔早期激素性股骨头坏死,具有较好的成骨治疗作用。转染Bcl-2的骨髓间充质干细胞加速了新骨形成,更有效对抗骨细胞凋亡,在短时间内完成坏死病灶的修复,对局部的骨坏死达到有效的治疗作用。 2.4.4 骨髓间充质干细胞的组织工程技术治疗 随着组织工程学技术的发展与进步,在临床多种疾病的治疗方面发挥着重要的作用。骨髓间充质干细胞联合工程学技术治疗股骨头坏死的机制是利用骨髓间充质干细胞能被诱导分化为成骨细胞的特性,结合骨组织工程的生物支架及诱导功能。骨移植材料需有很好的生物降解性及相容性,还需具备一定的可塑性和机械强度、多孔结构及材料表面微环境可调控性,可以诱导骨生成,并且还应具有骨传导和骨诱导的作用。支架材料的多孔结构,为细胞生长提供营养物质和代谢产物的传输通道,引导骨髓间充质干细胞的生长、增殖和分化,随着材料降解,新生骨组织逐步生长并取代骨移植材料。程中华等[36]将骨髓间充质干细胞与硼硅酸盐玻璃结合用于治疗兔股骨头坏死,术后4周X射线片显示植入材料区域密度较周边稍高,充填区界限清晰,周边有稍宽的反应带,8周见复合材料区稍高密度影与周围密度增高的骨组织界限难以分辨,周边反应带大部分消退,骨小梁渗入材料填充区,术后12周股骨头骨密度均匀,填充区域与周边骨组织无明显区别,原骨缺损区域密度和周边骨密度近似,无明显边界,充填区广泛分布有骨小梁,排列规则。LIVINGSTON等[37]将骨髓间充质干细胞与支架材料复合用于犬骨缺损修复,8周后植入物中有新骨形成,16周后骨缺损逐渐修复,这充分证明了骨髓间充质干细胞具有修复骨缺损的能力。各种人工合成材料层出不穷,新材料与骨髓间充质干细胞治疗早期股骨头坏死的研究正如火如荼进行,许多填充材料(纳米人工骨、羟基磷灰石、磷酸三钙等)联合骨髓间充质干细胞干预早期股骨头坏死取得良好疗效[38]。穆晓红等[39]利用纳米材料和组织工程技术,探索骨髓间充质干细胞和纳米晶胶原基骨修复材料在骨坏死修复中的作用,术后12周时幼稚的骨小梁占据部分填充区域,表面有较多的成骨细胞,部分充填区有较成熟的骨小梁分布,但比正常骨小梁粗、排列不够规则,大量板层骨和新生骨髓腔形成,材料大部分降解。多孔钽棒植入骨髓间充质干细胞在组织工程研究和临床应用中显示出较大的潜力[40]。 "
[1] VAISHYA R, AGARWAL AK, GUPTA N, et al. Sartorius muscle pedicle iliac bone graft for the treatment of avascular necrosis of femur head. J Hip Preserv Surg. 2016;3(3):215-222. [2] AMANATULLAH DF, STRAUSS EJ, DI CESARE PE. Current management options for osteonecrosis of the femoral head: part 1, diagnosis and nonoperative management. Am J Orthop (Belle Mead NJ). 2011;40(9):E186-192. [3] AMANATULLAH DF, STRAUSS EJ, DI CESARE PE. Current management options for osteonecrosis of the femoral head: part II, operative management. Am J Orthop (Belle Mead NJ). 2011;40(10):E216-225. [4] KUBO T, UESHIMA K, SAITO M, et al. Clinical and basic research on steroid-induced osteonecrosis of the femoral head in Japan. J Orthop Sci. 2016;21(4):407-413. [5] LARSON E, JONES LC, GOODMAN SB, et al. Early-stage osteonecrosis of the femoral head: where are we and where are we going in year 2018. Int Orthop. 2018;42(7):1723-1728. [6] MOYA-ANGELER J, GIANAKOS AL, VILLA JC, et al. Current concepts on osteonecrosis of the femoral head. World J Orthop. 2015;6(8):590-601. [7] SUGANO N, ATSUMI T, OHZONO K, et al. The 2001 revised criteria for diagnosis, classification, and staging of idiopathic osteonecrosis of the femoral head. J Orthop Sci. 2002;7(5): 601-605. [8] SOOHOO NF, VYAS S, MANUNGA J, et al. Cost-effectiveness analysis of core decompression. J Arthroplasty. 2006;21(5):670-681. [9] ROTH A, BECKMANN J, BOHNDORF K, et al. S3-Guideline non-traumatic adult femoral head necrosis. Arch Orthop Trauma Surg. 2016;136(2):165-174. [10] SAMPSON S, BOTTO-VAN BEMDEN A, AUFIERO D. Stem cell therapies for treatment of cartilage and bone disorders: osteoarthritis, avascular necrosis, and non-union fractures. PM R. 2015;7(4 Suppl):S26-S32. [11] BIANCO P, ROBEY PG, SIMMONS PJ. Mesenchymal stem cells: revisiting history, concepts, and assays. Cell Stem Cell. 2008;2(4):313-319. [12] DENG W, OBROCKA M, FISCHER I, et al. In vitro differentiation of human marrow stromal cells into early progenitors of neural cells by conditions that increase intracellular cyclic AMP. Biochem Biophys Res Commun. 2001;282(1):148-152. [13] 赵军,张晓峰,徐西林,等.骨髓间充质干细胞定向分化治疗股骨头坏死:应用效果与评价[J].中国组织工程研究,2019,23(13): 2127-2132. [14] 代学俊,岑蔼儿,张春梅,等.骨质疏松症抑制人间充质干细胞的成骨分化[J].中山大学学报(医学科学版),2014,35(5):723-729. [15] DERUBEIS AR, CANCEDDA R. Bone marrow stromal cells (BMSCs) in bone engineering: limitations and recent advances. Ann Biomed Eng. 2004;32(1):160-165. [16] VERONESI F, TORRICELLI P, DELLA BELLA E, et al. In vitro mutual interaction between tenocytes and adipose-derived mesenchymal stromal cells. Cytotherapy. 2015;17(2):215-223. [17] CHEN C, QU Z, YIN X, et al. Efficacy of umbilical cord-derived mesenchymal stem cell-based therapy for osteonecrosis of the femoral head: A three-year follow-up study. Mol Med Rep. 2016;14(5):4209-4215. [18] STEINBERG ME, LARCOM PG, STRAFFORD B, et al. Core decompression with bone grafting for osteonecrosis of the femoral head. Clin Orthop Relat Res. 2001;(386):71-78. [19] GANGJI V, DE MAERTELAER V, HAUZEUR JP. Autologous bone marrow cell implantation in the treatment of non-traumatic osteonecrosis of the femoral head: Five year follow-up of a prospective controlled study. Bone. 2011;49(5): 1005-1009. [20] MUTIJIMA E, DE MAERTELAER V, DEPREZ M, et al. The apoptosis of osteoblasts and osteocytes in femoral head osteonecrosis: its specificity and its distribution. Clin Rheumatol. 2014;33(12): 1791-1795. [21] HELBIG L, SIMANK HG, KROEBER M, et al. Core decompression combined with implantation of a demineralised bone matrix for non-traumatic osteonecrosis of the femoral head. Arch Orthop Trauma Surg. 2012;132(8): 1095-1103. [22] PAPAKOSTIDIS C, TOSOUNIDIS TH, JONES E, et al. The role of "cell therapy" in osteonecrosis of the femoral head. A systematic review of the literature and meta-analysis of 7 studies. Acta Orthop. 2016;87(1):72-78. [23] 王谦,黄国鑫,陈磊,等.髓芯减压联合自体骨髓间充质干细胞移植治疗股骨头坏死:安全和有效性的Meta分析[J].中国组织工程研究,2018,22(17):2733-2739. [24] SEN RK, TRIPATHY SK, AGGARWAL S, et al. Early results of core decompression and autologous bone marrow mononuclear cells instillation in femoral head osteonecrosis: a randomized control study. J Arthroplasty. 2012;27(5): 679-686. [25] HERNIGOU P, BEAUJEAN F. Treatment of osteonecrosis with autologous bone marrow grafting. Clin Orthop Relat Res. 2002;(405):14-23. [26] GANGJI V, HAUZEUR JP, MATOS C, et al. Treatment of osteonecrosis of the femoral head with implantation of autologous bone-marrow cells. A pilot study. J Bone Joint Surg Am. 2004;86(6):1153-1160. [27] 程少容,王仁法,高小玲,等.动态增强MRI定量分析股骨头缺血性坏死介入治疗后的血流变化[J].医学影像学杂志, 2006,16(9): 975-977. [28] 季卫锋,童培建,郑文标,等.骨髓多能干细胞动脉灌注治疗股骨头坏死的实验研究[J].中国中西医结合杂志,2004,24(11): 999-1002. [29] 童培建,叶福生,张善星,等.超选动脉骨髓基质干细胞灌注治疗非创伤性股骨头坏死中长期疗效分析[J].中国骨伤, 2014,27(7): 565-569. [30] MAO Q, JIN H, LIAO F, et al. The efficacy of targeted intraarterial delivery of concentrated autologous bone marrow containing mononuclear cells in the treatment of osteonecrosis of the femoral head: a five year follow-up study. Bone. 2013;57(2):509-516. [31] MA XW, CUI DP, ZHAO DW. Vascular endothelial growth factor/bone morphogenetic protein-2 bone marrow combined modification of the mesenchymal stem cells to repair the avascular necrosis of the femoral head. Int J Clin Exp Med. 2015;8(9):15528-15534. [32] 白志刚,巩凡,马军, 等.VEGF165基因转染兔骨髓间充质干细胞治疗兔激素性股骨头坏死的实验研究[J].宁夏医学杂志,2013, 35(10):892-895. [33] DING H, GAO YS, HU C, et al. HIF-1α transgenic bone marrow cells can promote tissue repair in cases of corticosteroid-induced osteonecrosis of the femoral head in rabbits. PLoS One. 2013;8(5):e63628. [34] HANG D, WANG Q, GUO C, et al. Treatment of osteonecrosis of the femoral head with VEGF165 transgenic bone marrow mesenchymal stem cells in mongrel dogs. Cells Tissues Organs. 2012;195(6):495-506. [35] 张立岩,孙新,田丹,等.Bcl-2基因转染骨髓干细胞治疗激素性股骨头坏死的疗效研究[J].中国现代医学杂志,2017,27(14):19-23. [36] 程中华,薛威,王李琴,等.骨髓间充质干细胞结合硼硅酸盐玻璃支架修复兔股骨头坏死[J].骨科,2017,8(2):121-126. [37] LIVINGSTON T, KADIYALI S, ELKALAY M, et al. Repair of canine segmental bone defects using all ogeneic mesenchymal stem cells. Transactions of the 47th Annual ORS meeting, 2001: 26. [38] 赵桥,肖东琴,杨飞.早期股骨头坏死的组织工程学治疗研究进展[J].西部医学, 2019,31(4):643-648. [39] 穆晓红,赵子义,徐林, 等.纳米材料支架与骨髓间充质干细胞构建纳米骨修复兔股骨头坏死[J].中国组织工程研究与临床康复, 2010,14(51):9582-9586. [40] LIU B, YANG F, WEI X, et al. An exploratory study of articular cartilage and subchondral bone reconstruction with bone marrow mesenchymal stem cells combined with porous tantalum/Bio-Gide collagen membrane in osteonecrosis of the femoral head. Mater Sci Eng C Mater Biol Appl. 2019;99: 1123-1132. [41] YU Z, FAN L, LI J, et al. Lithium chloride attenuates the abnormal osteogenic/adipogenic differentiation of bone marrow-derived mesenchymal stem cells obtained from rats with steroid-related osteonecrosis by activating the β-catenin pathway. Int J Mol Med. 2015;36(5):1264-1272. [42] KANG JS, SUH YJ, MOON KH, et al. Clinical efficiency of bone marrow mesenchymal stem cell implantation for osteonecrosis of the femoral head: a matched pair control study with simple core decompression. Stem Cell Res Ther. 2018;9(1):274. |
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