切换至 "中华医学电子期刊资源库"
高级检索
中华关节外科杂志(电子版)

中华关节外科杂志(电子版) ›› 2018, Vol. 12 ›› Issue (06) : 835 -841. doi: 10.3877/cma.j.issn.1674-134X.2018.06.017

所属专题： 文献；

综述

共培养体系在关节软骨组织工程中的应用研究
邹健宇1, 刘日许1, 郑仕聪1, 姚咏嫦1,†()   
  1. 1. 510120　广州医科大学附属第一医院骨关节外科，广东省骨科矫形技术及植入材料重点实验室
  • 收稿日期:2018-10-14 出版日期:2018-12-01
  • 通信作者: 姚咏嫦
  • 基金资助:
    广州市属高校科研项目重点项目(1201610097); 广州市科技计划项目一般项目(201804010479)

Application of co-culture system in articular cartilage tissue engineering

Jianyu Zou1, Rixu Liu1, Shicong Zheng1, Yongchang Yao1,†()   

  1. 1. Department of Joint Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China; Guangdong key laboratory of orthopaedic technology and implant materials, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China
  • Received:2018-10-14 Published:2018-12-01
  • Corresponding author: Yongchang Yao
  • About author:
    Corresponding author: Yao Yongchang, Email:
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

邹健宇, 刘日许, 郑仕聪, 姚咏嫦. 共培养体系在关节软骨组织工程中的应用研究[J]. 中华关节外科杂志(电子版), 2018, 12(06): 835-841.

Jianyu Zou, Rixu Liu, Shicong Zheng, Yongchang Yao. Application of co-culture system in articular cartilage tissue engineering[J]. Chinese Journal of Joint Surgery(Electronic Edition), 2018, 12(06): 835-841.

软骨组织工程是未来修复关节软骨的重要策略，但面临着软骨细胞数量不足，体外培养去分化以及分化方向难以控制等瓶颈。共培养体系的提出为这些问题提供了新的解决方式。一系列的研究发现，共培养体系可以阻止软骨细胞在体外培养的去分化现象，并促使已发生去分化的软骨细胞实现再分化，同时促进体系中干细胞的软骨分化以及抑制其肥大化进程。本综述通过对国内外应用在软骨组织工程的共培养研究进行概述，总结共培养体系对于软骨组织工程软骨形成的作用，同时探讨其积极作用的机制。

关键词: 共同培养技术, 软骨细胞, 组织工程

Cartilage tissue engineering appears as an important strategy for repairing articular cartilage. However, it faces the problems of insufficient number of chondrocytes, dedifferentiation in vitro, and difficulty in controlling the direction of differentiation. The co-culture system provides a new solution to these problems. A series of studies have reported that the co-culture system can prevent the dedifferentiation of chondrocytes cultured in vitro, promote the re-differentiation of dedifferentiated chondrocytes, and facilitate the chondrogenic differentiation of stem cells in the system as well as inhibit the process of hypertrophy. This review summarized the literatures about the application of co-culture system in cartilage tissue engineering, discussed the role of co-culture system in cartilage tissue engineering, and explored the underlying mechanism.

Key words: Coculture techniques, Chondrocytes, Tissue engineering
[1]
Lin Z, Willers C, Xu J , et al. The Chondrocyte: Biology and Clinical Application[J]. Tissue Eng Part A, 2006, 12(7): 1971-1984.
[2]
Lories RJ, Luyten FP. The bone-cartilage unit in osteoarthritis[J]. Nat Rev Rheumatol, 2011, 7(1): 43-49.
[3]
Ding C, Jones G, Wluka AE, et al. What can we learn about osteoarthritis by studying a healthy person against a person with early onset of disease? [J/OL]. Curr Opin Rheumatol, 2010，22(5)：520-7. doi: 10.1097/BOR.0b013e32833b90e9.
[4]
Carnes J, Stannus O, Cicuttini FM, et al. Knee cartilage defects in a sample of older adults: natural history, clinical significance and factors influencing change over 2.9 years[J]. Osteoarthr Cartilage, 2012, 20(12): 1541-1547.
[5]
Falah M, Nierenberg G, Soudry M, et al. Treatment of articular cartilage lesions of the knee[J]. Int Orthop, 2010, 34(5): 621-630.
[6]
Makris EA, Gomoll AH, Malizos KN, et al. Repair and tissue engineering techniques for articular cartilage[J]. Nat Rev Rheumatol, 2015, 11(1): 21-34.
[7]
Peterson L, Vasiliadis HS, Brittberg M, et al. Autologous chondrocyte implantation a long-term follow-up[J/OL]. Am J Sport Med, 2010，38(6)：1117-24. doi: 10.1177/0363546509357915.
[8]
Cole BJ, Pascual-Garrido C, Grumet RC. Surgical management of articular cartilage defects in the knee[J/OL]. J Bone Joint Surg Am, 2010，59(7): 181. doi: 10.1016/S0735-1097(15)62028-9
[9]
Ahmed TA, Hincke MT. Mesenchymal stem cell-based tissue engineering strategies for repair of articular cartilage[J]. Histol Histopathol, 2014, 29(6): 669-689.
[10]
Dai WD, Kawazoe N, Lin XT, et al. The influence of structural design of PLGA/collagen hybrid scaffolds in cartilage tissue engineering[J]. Biomaterials, 2010, 31(8): 2141-2152.
[11]
Ahmed N, Dreier R, Göpferich A, et al. Soluble signalling factors derived from differentiated cartilage tissue affect chondrogenic differentiation of rat adult marrow stromal cells[J]. Cell Physiol Biochem, 2007, 20(5)：665-678.
[12]
Fischer J, Dickhut A, Rickert M, et al. Human articular chondrocytes secrete parathyroid hormone-related protein and inhibit hypertrophy of mesenchymal stem cells in coculture during chondrogenesis.[J]. Arthritis Rheum, 2014, 62(9)：2696-2706.
[13]
李丽艳，黄金中. 杜江．转化生长因子β1诱导骨髓间充质干细胞向软骨细胞分化[J]．中国组织工程研究，2010，14(1)：38-41.
[14]
Tsuchiya K, Chen G, Ushida T , et al. The effect of coculture of chondrocytes with mesenchymal stem cells on their cartilaginous phenotype in vitro[J]. Mat Sci Eng C-Mater, 2004, 24(3)：391-396.
[15]
Holtzer H, Abbott J, Lash J , et al. The loss of phenotypic traits by differentiaed cells in vitro, I. dedifferentiation of cartilage cells[J]. Proc Natl Acad Sci U S A, 1960, 46(12): 1533-1542.
[16]
Goessler UR, Bugert P, Bieback K, et al. Expression of collagen and fiber-associated proteins in human septal cartilage during in vitro dedifferentiation[J]. Int J Mol Med, 2004, 14(6): 1015-1022.
[17]
徐磊，叶朝阳，周燕，等．体外传代培养兔关节软骨细胞的去分化现象[J]．中国组织工程研究，2013，17(20)：3626-3634.
[18]
Duan L, Ma B, Liang YJ, et al. Cytokine networking of chondrocyte dedifferentiation in vitro and its implications for cell-based cartilage therapy[J]. Am J Transl Res, 2015, 7(2): 194-208.
[19]
Maribel Mata-Miranda M, Maria Martinez-Martinez CA, Enrique Paredes-Gonzalez LA. Morphological, genetic and phenotypic comparison between human articular chondrocytes and cultured chondrocytes[J]. Histochem Cell Biol, 2016, 146(2): 183-189.
[20]
Qing C, Weiding C, Weimin F. Co-culture of chondrocytes and bone marrow mesenchymal stem cells in vitro enhances the expression of cartilaginous extracellular matrix components[J/OL]. Braz J Med Biol Res, 2011，44(4)：303-10. doi：10.1590/S0100-879X2011007500026.
[21]
Lettry V, Hosoya K, Takagi S, et al. Coculture of equine mesenchymal stem cells and mature equine articular chondrocytes results in improved chondrogenic differentiation of the stem cells[J]. Jpn J Vet Res, 2010, 58(1): 5-15.
[22]
Xu L, Wang Q, Xu F, et al. Mesenchymal stem cells downregulate articular chondrocyte differentiation in noncontact coculture systems: implications in cartilage tissue regeneration[J]. Stem Cells Dev, 2013, 22(11): 1657-1669.
[23]
谢鹏. 张仲文．自体骨髓间充质干细胞和同种异体软骨细胞共培养优化软骨组织工程种子的细胞源[J]．中国组织工程研究，2012，16(14)：2509-2514.
[24]
关炼雄，段莉，黄江鸿，等．软骨细胞去分化研究进展[J]．国际骨科学杂志，2014，35(4)：250-253.
[25]
刘瑾春，刘霞，曹谊林．软骨细胞培养中细胞去分化和再分化研究进展[J]．中华整形外科杂志，2011，27(4)：318-320.
[26]
Gan L, Kandel RA. In vitro cartilage tissue formation by co-culture of primary and passaged chondrocytes[J]. Tissue Eng, 2007, 13(4): 831-842.
[27]
Doege K J, Sasaki M, Kimura T , et al. Complete coding sequence and deduced primary structure of the human cartilage large aggregating proteoglycan, aggrecan. Human-specific repeats, and additional alternatively spliced forms[J]. J Biol Chem, 1991, 266(2)：894-902.
[28]
Meretoja VV, Dahlin RL, Wright S, et al. Articular chondrocyte redifferentiation in 3D co-cultures with mesenchymal stem cells[J/OL]. Tissue Eng Part C Methods, 2014 ，20(6)：514-23. doi: 10.1089/ten.tec.2013.0532.
[29]
Meretoja VV, Dahlin RL, Kasper FK, et al. Enhanced chondrogenesis in co-cultures with articular chondrocytes and mesenchymal stem cells[J/OL]. Biomaterials, 2012，33(27)：6362-9. doi: 10.1016/j.biomaterials.2012.05.042.
[30]
Acharya C, Adesida A, Zajac P, et al. Enhanced chondrocyte proliferation and mesenchymal stromal cells chondrogenesis in coculture pellets mediate improved cartilage formation[J]. J Cell Physiol, 2012 ，227(1)：88-97. doi: 10.1002/jcp.22706.
[31]
张艳，柴岗，刘伟，等．软骨细胞老化特征及机制的研究进展[J]．上海第二医科大学学报，2004，24(4)：322-325.
[32]
Sailor LZ, Morris EA. Recombinant human bone morphogenetic protein-2 maintains the articular chondrocyte phenotype in long-term culture[J]. J Orthop Res, 1996, 14(6): 937-945.
[33]
Yamamoto Y, Mochida J, Sakai D, et al. Upregulation of the viability of nucleus pulposus cells by bone marrow-derived stromal cells: significance of direct cell-to-cell contact in coculture system[J]. Spine (Phila Pa 1976), 2004, 29(14): 1508-1514.
[34]
孙明林，朱雷，吕丹．Ⅱ型胶原蛋白对兔去分化软骨细胞再分化的作用[J]．中国修复重建外科杂志，2010(10)：1244-1248.
[35]
Liu X, Sun HY, Yan D, et al. In vivo ectopic chondrogenesis of BMSCs directed by mature chondrocytes[J]. Biomaterials, 2010, 31(36): 9406-9414.
[36]
Lee JS, Im GI. Influence of chondrocytes on the chondrogenic differentiation of adipose stem cells[J]. Tissue Eng Part A, 2010, 16(12): 3569-3577.
[37]
Zuo Q, Cui W, Liu F, et al. Co-cultivated mesenchymal stem cells support chondrocytic differentiation of articular chondrocytes[J]. Int Orthop, 2013, 37(4): 747-752.
[38]
White TW, Bruzzone R. Multiple connexin proteins in single intercellular channels: Connexin compatibility and functional Consequences[J]. J Bioenerg Biomembr, 1996, 28(4): 339-350.
[39]
Chen WH, Lai MT, Wu AT, et al. In vitro stage-specific chondrogenesis of mesenchymal stem cells committed to chondrocytes[J]. Arthritis Rheum, 2009, 60(2): 450-459.
[40]
Wu L, Leijten JC, Georgi N, et al. Trophic effects of mesenchymal stem cells increase chondrocyte proliferation and matrix formation[J]. Tissue Eng Part A, 2011, 17(9/10): 1425-1436.
[41]
Akiyama H, Chaboissier MC, Martin JF, et al. The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6[J]. Genes Dev, 2002, 16(21): 2813-2828.
[42]
Schmid TM, Linsenmayer TF. Immunohistochemical localization of short chain cartilage collagen (type X) in avian tissues[J]. J Cell Biol, 1985, 100(2): 598-605.
[43]
Wysokinski D, Pawlowska E, Blasiak J. RUNX2: a master bone growth regulator that may be involved in the DNA damage response[J/OL]. DNA Cell Biol, 2015，34(5)：305-15. doi: 10.1089/dna.2014.2688.
[44]
杜腾飞，刘国明，郭小美，等．甲状旁腺激素对大鼠牵张成骨过程中ONC、OPN、C-FOS、COL1、VEGF、RUNX2、ALP基因表达的影响[J]．山东大学学报(医学版)，2015，53(03)：32-35.
[45]
Winter A, Breit S, Parsch D, et al. Cartilage-like gene expression in differentiated human stem cell spheroids: a comparison of bone marrow-derived and adipose tissue-derived stromal cells[J]. Arthritis Rheum, 2003, 48(2): 418-429.
[46]
Pelttari K, Winter A, Steck E, et al. Premature induction of hypertrophy during in vitro chondrogenesis of human mesenchymal stem cells correlates with calcification and vascular invasion after ectopic transplantation in SCID mice[J]. Arthritis Rheum, 2006, 54(10): 3254-3266.
[47]
Zhang F, Su K, Fang Y, et al. A mixed co-culture of mesenchymal stem cells and transgenic chondrocytes in alginate hydrogel for cartilage tissue engineering[J]. J Tissue Eng Regen Med, 2015, 9(1): 77-84.
[48]
Cooke ME, Allon AA, Cheng T, et al. Structured three-dimensional co-culture of mesenchymal stem cells with chondrocytes promotes chondrogenic differentiation without hypertrophy[J/OL]. Osteoarthr Cartilage, 2011，19(10)：1210-8. doi: 10.1016/j.joca.2011.07.005.
[49]
Aung A, Gupta G, Majid G, et al. Osteoarthritic chondrocyte-secreted morphogens induce chondrogenic differentiation of human mesenchymal stem cells[J]. Arthritis Rheum, 2011, 63(1): 148-158.
[50]
Giovannini S, Diazromero J, Aigner T , et al. Micromass co-culture of human articular chondrocytes and human bone marrow mesenchymal stem cells to investigate stable neocartilage tissue formation in vitro.[J]. Eur Cell Mater. 2010，20：245-259.
[51]
Sabatino MA, Santoro R, Gueven SA, et al. Cartilage graft engineering by co-culturing primary human articular chondrocytes with human bone marrow stromal cells[J]. J Tissue Eng Regen Med, 2015, 9(12): 1394-1403.
[52]
Zhao X, Hwang NS, Bichara DA, et al. Chondrogenesis by bone marrow-derived mesenchymal stem cells grown in chondrocyte-conditioned medium for auricular Reconstruction[J]. J Tissue Eng Regen Med, 2017, 11(10): 2763-2773.
[53]
Zhang L, Zheng L, Fan HS, et al. A scaffold-filter model for studying the chondrogenic differentiation of stem cells in vitro[J]. Mater Sci Eng C Mater Biol Appl, 2017, 70(Pt 2): 962-968.
[54]
Islam MA, Hansen AK, Mennan C, et al. Mesenchymal stromal cells from human umbilical cords display poor chondrogenic potential in scaffold-free three dimensional cultures[J]. Eur Cell Mater, 2016, 31：407-24.
[55]
Goldring SR, Dayer JM, Krane SM. Rheumatoid synovial cell hormone responses modulated by cell-cell interactions[J]. Inflammation, 1984, 8(1): 107-121.
[56]
Furumatsu T, Tsuda M, Taniguchi N, et al. Smad3 induces chondrogenesis through the activation of SOX9 via CREB-binding protein/p300 recruitment[J]. J Biol Chem, 2005, 280(9): 8343-8350.
[57]
Lluís Quintana, Nieden NIZ, Semino CE. Morphogenetic and regulatory mechanisms during developmental chondrogenesis: new paradigms for cartilage tissue engineering[J]. Tissue Eng Part B Rev, 2009, 15(1)：29.
[58]
Zhang M, Zhou Q, Liang QQ, et al. IGF-1 regulation of type II collagen and MMP-13 expression in rat endplate chondrocytes via distinct signaling pathways[J/OL]. Osteoarthr Cartilage, 2009 Jan；17(1)：100-106. doi: 10.1016/j.joca.2008.05.007.
[59]
Terada N, Hamazaki T, Oka M, et al. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion[J]. Nature, 2002, 416(6880): 542-545.
[60]
Djouad F, Delorme B, Maurice M, et al. Microenvironmental changes during differentiation of mesenchymal stem cells towards chondrocytes[J]. Arthritis Res Ther, 2007, 9(2): 1-12.
[61]
Guillotin B, Bourget C, Remy-Zolgadri M, et al. Human primary endothelial cells stimulate human osteoprogenitor cell differentiation[J]. Cell Physiol Biochem. 2004，14(4－6)：325-332.
[62]
李超然，黄桂林，王帅．间充质干细胞来源外泌体促进损伤组织修复与再生的应用与进展[J]．中国组织工程研究，2018，22(1)：133-139.
[63]
Zhang J, Liu X, Li H , et al. Exosomes/tricalcium phosphate combination scaffolds can enhance bone regeneration by activating the PI3K/Akt signaling pathway[J/OL]. Stem Cell Res Ther, 2016，7(1)：136. doi: 10.1186/s13287-016-0391-3.
[64]
Qi X, Zhang J, Yuan H , et al. Exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem cells repair critical-sized bone defects through enhanced angiogenesis and osteogenesis in osteoporotic rats[J]. Int J Biol Sci, 2016, 12(7)：836-849.
[65]
Furuta T, Miyaki S, Ishitobi H , et al. Mesenchymal stem cell-derived exosomes promote fracture healing in a mouse model.[J/OL]. Stem Cells Transl Med, 2016，5(12)：1620-1630. doi: 10.5966/sctm.2015-0285
[66]
Tao SC, Yuan T, Zhang YL, et al. Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model.[J]. Theranostics, 2017, 7(1)：180-195.
[67]
Higuera GA, Hendriks JA, Van Dalum JA, et al. In vivo screening of extracellular matrix components produced under multiple experimental conditions implanted in one animal[J]. Integr Biol, 2013, 5(6): 889-898.
[68]
Lv XJ, Zhou GD, Liu X, et al. Chondrogenesis by co-culture of adipose-derived stromal cells and chondrocytes in vitro[J]. Connect Tissue Res, 2012, 53(6): 492-497.
[69]
Critchley SE, Eswaramoorthy R, Kelly DJ. Low oxygen conditions promote synergistic increases in chondrogenesis during co-culture of human osteoarthritic stem cells and chondrocytes[J/OL]. J Tissue Eng Regen Med. 2018，12(4)：1074-1084. doi: 10.1002/term.2608.
[70]
Ito A, Aoyama T, Tajino J, et al. Effects of culturing temperature on extracellular matrix formation and redifferentiation of expanded human chondrocyte [J/OL]. Osteoarthr Cartilage, 2014, 22(S): S170. doi：10.1016/j.joca.2014.02.318
[71]
He XM, Feng B, Huang CP, et al. Electrospun gelatin/polycaprolactone nanofibrous membranes combined with a coculture of bone marrow stromal cells and chondrocytes for cartilage engineering[J/OL]. Int J Nanomedicine. 2015，10：2089-2099. doi: 10.2147/IJN.S79461.
[72]
Li D, Zhu L, Liu Y, et al. Stable subcutaneous cartilage regeneration of bone marrow stromal cells directed by chondrocyte sheet[J/OL]. Acta Biomater, 2017，54：321-332. doi: 10.1016/j.actbio.2017.03.031.
[73]
Olivos-Meza A, Martínez CV, Díaz BO, et al. Co-culture of dedifferentiated and primary human chondrocytes obtained from cadaveric donor enhance the histological quality of repair tissue: an in-vivo animal study[J/OL]. Cell Tissue Bank, 2017，18(3)：369-381. doi: 10.1007/s10561-017-9635-4.
[1] 罗璠, 饶志涛. 机械敏感蛋白Piezo1介导创伤后骨关节炎的作用及机制[J]. 中华关节外科杂志(电子版), 2023, 17(04): 528-533.
[2] 陈严城, 符培亮. 组织工程技术在骨软骨缺损中应用的研究进展[J]. 中华关节外科杂志(电子版), 2023, 17(03): 376-384.
[3] 钱嘉天, 符培亮. 3D打印脱细胞的细胞外基质修复软骨缺损的研究进展[J]. 中华关节外科杂志(电子版), 2023, 17(03): 368-375.
[4] 陈曦, 刘畅, 李萍, 李雨航, 陈彦斌, 王昆. 肩峰下滑囊的解剖结构和功能与临床意义[J]. 中华关节外科杂志(电子版), 2022, 16(03): 337-342.
[5] 傅子财, 黄勇, 陈斐, 刘澍雨, 朱伟民. 间充质干细胞来源外泌体在骨关节炎治疗中的研究进展[J]. 中华关节外科杂志(电子版), 2022, 16(02): 196-201.
[6] 王雪, 程微, 苏建东. 微针法表皮移植应用的新进展[J]. 中华损伤与修复杂志(电子版), 2023, 18(03): 270-273.
[7] 蒯贤东, 郑国爽, 杨佳慧, 赵德伟. 用于关节软骨缺损修复的壳聚糖复合支架的研究进展[J]. 中华损伤与修复杂志(电子版), 2022, 17(06): 535-539.
[8] 刘梦柔, 刘沛东, 张城铭, 刘阳, 李鹏翠, 杨自权. 基于文献计量学与可视化分析的骨组织工程支架材料的全球研究现状及发展趋势[J]. 中华损伤与修复杂志(电子版), 2022, 17(05): 411-420.
[9] 王湘滔, 张爱娟, 王万春, 王芳萍, 徐颖婕, 孟洋. 中药白及在口腔疾病中的研究与应用[J]. 中华口腔医学研究杂志(电子版), 2023, 17(05): 371-375.
[10] 孙艺琪, 史宏灿. 纳米技术在气管移植物中的应用[J]. 中华移植杂志(电子版), 2022, 16(05): 309-313.
[11] 钟文文, 李科, 刘碧好, 蔡炳, 脱颖, 叶雷, 马波, 瞿虎, 汪中扬, 王德娟, 邱剑光. 不同比例聚乳酸/丝素蛋白复合支架在兔尿道缺损修复中的疗效[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(05): 516-522.
[12] 林诗雯, 孙慧, 陈娜娜, 朱聪. 共培养促神经化策略在组织工程骨构建中的研究进展[J]. 中华细胞与干细胞杂志(电子版), 2022, 12(05): 293-299.
[13] 张郭, 慈海, 周牧冉, 孙家明, 郭亮. 仿生聚己内酯支架用于乳房组织工程的可行性研究[J]. 中华细胞与干细胞杂志(电子版), 2022, 12(04): 215-223.
[14] 周莹芊, 汪振星, 张一帆, 孙家明, 曹谊林. 模块化与血管化组织工程技术[J]. 中华细胞与干细胞杂志(电子版), 2022, 12(03): 161-166.
[15] 杜凯玥, 袁博伟, 洪晶. 水凝胶在角膜修复中的应用研究进展[J]. 中华眼科医学杂志(电子版), 2022, 12(05): 298-304.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号