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关节软骨属于透明软骨,其表面光滑,具有减小摩擦、保护软骨下骨、增加关节运动承载负荷的作用。由于关节软骨是一种无血管组织,主要依靠关节液营养,其自身修复、再生能力很低。当创伤、肿瘤、炎症等病因导致关节软骨缺损及损伤后,常引起关节疼痛、不稳和僵硬等症状,如果治疗不及时或治疗方法不恰当,后期常继发成为骨性关节炎,最终患者不得不接受人工关节置换[1]。目前临床上常用的骨髓刺激技术、自体或异体骨软骨移植、骨膜软骨膜移植等治疗方法存在纤维化、退化或者二期骨化的问题,都难以取得理想的效果[2]。
以间充质干细胞(mesenchymal stem cells,MSCs)移植治疗为基础的软骨组织工程是近年来研究的热点。目前认为MSCs取材方便、体外培养简单、增殖和成软骨能力强,是软骨组织工程首选的“种子”细胞[3-5]。将MSCs移植到软骨缺损区域诱导自体软骨的形成成为一种最有前景的治疗方法。
MSCs移植后,为了评估其移植的效果,明确外源性MSCs在软骨缺损再生修复中所扮演的角色,MSCs移植的示踪研究是非常必要的。传统的细胞示踪方法如荧光染料标记法、同位素标记法等需要在离体状态下行组织学切片分析和鉴定,不利于在活体内连续动态的跟踪观察,更不适于临床,具有较大的局限性。
MRI具有无创、无电离辐射、时间及空间分辨率高、软组织对比度好等优点,并能对监测对象进行三维重构,是广泛接受的无创评价关节软骨损伤修复的最佳检查方法[6-7]。协同MRI对比剂,MRI可作为动态监测MSCs的移植和迁移情况的理想手段[8],能同时提供关节软骨精确的解剖结构及生物化学特征。本文对近年来MR示踪技术在MSCs移植治疗软骨缺损中的应用作一综述。
MR示踪技术在干细胞移植治疗软骨缺损中的研究进展
The progress of magnetic resonance cell tracing technique in stem cells transplantation treatment of cartilage defects
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摘要: 关节软骨缺损临床十分常见, 但目前的治疗方法均存在修复不完全的缺陷。间充质干细胞移植治疗的发展为再生修复关节软骨缺损提供了新的治疗策略, 但是作为组织修复执行者的干细胞移植后的在体迁徙分布、增殖及转归过程, 目前尚无安全无创、实时动态的监测手段, 因此难以明确外源性干细胞在关节软骨缺损再生修复中所扮演的角色。而MR在体示踪细胞技术为解决上述问题提供了新思路。MRI具有无创、无电离辐射、时间空间分辨率高、对比度好等优点, 协同MRI对比剂, 既可无创提供关节软骨的详细解剖结构信息, 还可动态评估移植干细胞的归宿。笔者就MR示踪技术在干细胞移植治疗软骨缺损中的最新研究进展进行综述, 探讨其优势、局限性及未来前景。Abstract: Articular cartilage defects are common and caused by many reasons. However, treatments including conservative treatment, joint debridement, autologous or allogeneic bone cartilage transplantation and artificial joint replacement have obvious limitations such as incomplete repair. Mesenchymal stem cells(MSCs) transplantation therapy is considered as a new and effective therapy proposal of articular cartilage defects in future. But it is difficult to know about the role MSCs played in repairing process because of the lack of methods regarding the efficient and noninvasive technique to monitor the in vivo behavior of delivered cells in host tissue. Recently, MRI in vivo tracking of labeled cells technology provides a new train of thought. MRI molecular imaging can not only noninvasively provide anatomical information of articular cartilage, but also evaluate the fate of transplanted stem cells. The novel progress of magnetic resonance cell tracing technique in stem cells transplantation treatment of cartilage defects was reviewed, and the strengths, limitations and prospect of MR tracing technique were explored in this review.
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[1] Centers for Disease Control and Prevention(CDC). Prevalence of doctor-diagnosed arthritis and arthritis-attributable activity limitation--United States, 2010-2012[J]. MMWR Morb Mortal Wkly Rep, 2013, 62(44):869-873. [2] Bouwmeester PS, Kuijer R, Homminga JN, et al. A retrospective analysis of two Independent prospective cartilage repair studies:autogenousperichondrial grafting versus subchondral drilling 10 year post-surgery[J]. J Orthop Res, 2002, 20(2):267-273. [3] Gardner OF, Archer CW, Alini M, et al. Chondrogenesis of mesenchymal stem cells for cartilage tissue engineering[J]. Histol Histopathol, 2013, 28(1):23-42. [4] Malgieri A, Kantzari E, Patrizi MP, et al. Bone marrow and umbilical cord blood human mesenchymal stem cells:state of the art[J]. Int J Clin Exp Med, 2010, 3(4):248-269. [5] Gimble JM, Grayson W, Guilak F, et al. Adipose tissue as a stem cell source for musculoskeletal regeneration[J]. Front Biosci(Schol Ed), 2011, 3:69-81. [6] Roemer FW, Crema MD, Trattnig SA. Advances in imaging of osteoarthritis and cartilage[J]. Radiology, 2011, 260(2):332-354. [7] 侯志超, 孙剑, 甄俊平, 等.关节软骨损伤修复的MRI评价[J].国际医学放射学杂志, 2011, 34(5):456-460. doi: 10.3784/j.issn.1674-1897.2011.05.Z0510
[8] Cromer Berman SM, Walczak P, Bulte JW. Tracking stem cells using magnetic nanoparticles[J]. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2011, 3(4):343-355. doi: 10.1002/wnan.140 [9] Haleem AM, El Singergy AA, Sabry D, et al. The clinical use of human Culture-Expanded autologous bone marrow mesenchymal stem cells transplanted on Platelet-Rich fibrin glue in the treatment of articular cartilage defects:a pilot study and preliminary results[J]. Cartilage, 2010, 1(4):253-261. doi: 10.1177/1947603510366027 [10] Emadedin M, Aghdami N, Taghiyar L, et al. Intra-articular injection of autologous mesenchymal stem cells in six patients with knee osteoarthritis[J]. Arch Iran Med, 2012, 15(7):422-428. [11] Bulte JW. In vivo MRI cell tracking:clinical studies[J]. AJR Am J Roentgenology, 2009, 193(2):314-325. doi: 10.2214/AJR.09.3107 [12] Nejadnik H, Henning TD, Thuy D, et al. MR imaging features of Gadofluorine-Labeled Matrix-Associated stem cell implants in cartilage defects[J/OL]. PLoS One, 2012, 7(12): e49971[2015-03-01].http://journals. plos. org/plosone/article?id=10. 1371/journal. pone. 0049971. [13] Nedopil A, Klenk C, Kim C, et al. MR signal characteristics of viable and apoptotic human mesenchymal stem cells in matrix-associated stem cell implants for treatment of osteoarthritis[J]. Invest Radiol, 2010, 45(10):634-640. doi: 10.1097/RLI.0b013e3181ed566c [14] Mathiasen AB, Hansen L, Friis T, et al. Optimal labeling dose, labeling time, and magnetic resonance imaging detection limits of ultrasmall superparamagnetic iron-oxide nanoparticle labeled mesenchymal stromal cells[J/OL]. Stem Cells Int, 2013, 2013: 353105[2015-03-01]. http://www. hindawi. com/journals/sci/2013/353105/. [15] Van Buul GM, Kotek G, Wielopolski PA, et al. Clinically translatable cell tracking and quantification by MRI in cartilage repair using superparamagnetic Iron oxides[J/OL]. PLoS One, 2011, 6(2): e17001[2015-03-01].http://journals. plos. org/plosone/article?id=10. 1371/journal. pone. 0017001. [16] Nedopil AJ, Mandrussow LG, Daldrup-Link HE. Implantation of ferumoxides labeled human mesenchymal stem cells in cartilage defects[J/OL]. J Vis Exp, 2010, (38): 1793[2015-03-01]. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2900275. [17] Henning TD, Gawande R, Khurana A, et al. Magnetic resonance imaging of Ferumoxide-Labeled mesenchymal stem cells in cartilage defects:in vitro and in vivo investigations[J]. Mol Imaging, 2012, 11(3):197-209. [18] Khurana A, Nejadnik H, Chapelin F, et al. Ferumoxytol:a new, clinically applicable label for stem cell tracking in arthritic joints with MRI[J]. Nanomedicine, 2013, 8(12):1969-1983. doi: 10.2217/nnm.12.198 [19] Jing XH, Yang L, Duan XJ, et al. In vivo Mr imaging tracking of magnetic Iron oxide nanoparticle labeled, engineered, autologous bone marrow mesenchymal stem cells following intra-articular injection[J]. Joint Bone Spine, 2008, 75(4):432-438. doi: 10.1016/j.jbspin.2007.09.013 [20] Kamei G, Kobayashi T, Ohkawa SA, et al. Articular cartilage repair with magnetic mesenchymal stem cells[J]. Am J Sports Med, 2013, 41(6):1255-1264. doi: 10.1177/0363546513483270 [21] Khurana A, Chapelin F, Beck G, et al. Iron administration before stem cell harvest enables Mr imaging tracking after transplantation[J]. Radiology, 2013, 269(1):186-197. [22] Bonnemain B. Superparamagnetic agents in magnetic resonance imaging:physicochemical characteristics and clinical applications. A review[J]. J Drug Target, 1998, 6(3):167-174. doi: 10.3109/10611869808997890
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