国际口腔医学杂志

国际口腔医学杂志 ›› 2020, Vol. 47 ›› Issue (3): 270-277.doi: 10.7518/gjkq.2020023

• 间充质干细胞专栏 • 上一篇    下一篇

生长因子诱导间充质干细胞三维体外软骨形成的研究进展

朱明静,张清彬()   

  1. 广州医科大学附属口腔医院颞下颌关节科,广州口腔疾病研究所,口腔医学重点实验室 广州 510140
  • 收稿日期:2019-08-12 修回日期:2019-11-26 出版日期:2020-05-01 发布日期:2020-05-08
  • 通讯作者: 张清彬
  • 作者简介:朱明静,硕士,Email：mirrorzhumingjing@163.com

Comparative review of growth factors inducing 3D in vitro cartilage formation of mesenchymal stem cells

Zhu Mingjing,Zhang Qingbin()   

  1. Key Laboratory of Oral Medicine, Guangzhou 510140, China
  • Received:2019-08-12 Revised:2019-11-26 Online:2020-05-01 Published:2020-05-08
  • Contact: Qingbin Zhang

RichHTML

63

PDF (PC)

210

摘要：

间充质干细胞软骨向分化的潜能已被广泛研究,并且已经表明这些干细胞的软骨形成潜能彼此不同。通常,软骨诱导最常见的生长因子来自转化生长因子（TGF）-β超家族。对文献的全面回顾表明,在含有地塞米松和TGF-β3的培养基中,三维培养中的间充质干细胞似乎表现出较高的软骨形成潜力。一些报道还表明加入TGF-β1、TGF-β2和TGF-β3,骨形态发生蛋白（BMP）-2、BMP-4、BMP-6、BMP-7和BMP-9,以及其他类型的细胞因子如成纤维细胞生长因子-2、糖皮质激素、胰岛素样生长因子-1等,也促进间充质干细胞软骨形成分化,但这些结果仍未得到一致支持。然而,迄今为止,目前的制剂并不是总会诱导间充质干细胞向成软骨稳定分化。本文综述了多种生长因子单独和组合对间充质干细胞三维体外软骨向分化影响的研究。

关键词: 间充质干细胞, 软骨向分化, 生长因子, 转化生长因子, 骨形态发生蛋白

Abstract:

The ability of marrow-derived mesenchymal stem cells (MSCs) to undergo chondrogenic differentiation has been studied extensively. The chondrogenic potential of these stem cells differs from one another. In general, the most common growth factors for chondrogenic induction originate from the transforming growth factor (TGF) -β superfamily. A thorough review of literature indicates that MSCs exhibit the highest chondrogenic potential in 3D culture in the medium containing dexamethasone and TGF-β3. Several reports indicated that the addition of TGF-β1, TGF-β2 and TGF-β3; bone morphogenetic protein (BMP)-2, BMP-4, BMP-6, BMP-7 and BMP-9; and several types of fibroblast growth factor-2. Glucocorticoids and insulin-like growth factor-1 promote MSCs for chondrogenic differentiation, but these results are still not consistently supported. However, to date, current formulations do not always induce the stable differentiation of MSC cartilages. In this paper, the effects of each growth factor alone and in combination on the 3D in vitro cartilage differentiation of MSCs were reviewed.

Key words: mesenchymal stem cell, chondrogenic differentiation, growth factor, transforming growth factor, bone morphogenetic protein

中图分类号: 

  • Q254
[1] Vayas R, Reyes R, Rodríguez-Évora M , et al. Eva-luation of the effectiveness of a bMSC and BMP-2 polymeric trilayer system in cartilage repair[J]. Biomed Mater, 2017,12(4):045001.
doi: 10.1088/1748-605X/aa6f1c pmid: 28675146
[2] Vukicevic S, Grgurevic L . BMP-6 and mesenchymal stem cell differentiation[J]. Cytokine Growth Factor Rev, 2009,20(5/6):441-448.
doi: 10.1016/j.cytogfr.2009.10.020 pmid: 19900832
[3] Puetzer JL, Petitte JN, Loboa EG . Comparative review of growth factors for induction of three-dimensional in vitro chondrogenesis in human mesenchymal stem cells isolated from bone marrow and adipose tissue[J]. Tissue Eng Part B Rev, 2010,16(4):435-444.
doi: 10.1089/ten.TEB.2009.0705 pmid: 20196646
[4] Barry F, Boynton RE, Liu B , et al. Chondrogenic differentiation of mesenchymal stem cells from bone marrow: differentiation-dependent gene expression of matrix components[J]. Exp Cell Res, 2001,268(2):189-200.
doi: 10.1006/excr.2001.5278 pmid: 11478845
[5] 李乔乔, 吴振强, 张丽君 . 骨髓间充质干细胞的定向分化潜能[J]. 中国组织工程研究, 2017,21(25):4082-4087.
Li QQ, Wu ZQ, Zhang LJ . Directional differentiation of bone marrow mesenchymal stem cells[J]. Chin J Tissue Eng Res, 2017,21(25):4082-4087.
[6] Yue DY, Zhang MX, Lu J , et al. The rate of fluid shear stress is a potent regulator for the differen-tiation of mesenchymal stem cells[J]. J Cell Physiol, 2019. doi: 10.1002/jcp.28296.
doi: 10.1002/jcp.28296 pmid: 30784070
[7] Chen XY, Qin ZN, Zhao JM , et al. Pulsed magnetic field stimuli can promote chondrogenic differentia-tion of superparamagnetic iron oxide nanoparticles-labeled mesenchymal stem cells in rats[J]. J Biomed Nanotechnol, 2018,14(12):2135-2145.
doi: 10.1166/jbn.2018.2644 pmid: 30305220
[8] Nasrabadi D, Rezaeiani S, Eslaminejad MB , et al. Improved protocol for chondrogenic differentiation of bone marrow derived mesenchymal stem cells- effect of PTHrP and FGF-2 on TGFβ1/BMP2-induced chondrocytes hypertrophy[J]. Stem Cell Rev Rep, 2018,14(5):755-766.
doi: 10.1007/s12015-018-9816-y pmid: 29691795
[9] Bernardo ME, Emons JA, Karperien M , et al. Human mesenchymal stem cells derived from bone marrow display a better chondrogenic differentiation com-pared with other sources[J]. Connect Tissue Res, 2007,48(3):132-140.
doi: 10.1080/03008200701228464 pmid: 17522996
[10] Steadman JR, Rodkey WG, Rodrigo JJ . Microfracture: surgical technique and rehabilitation to treat chondral defects[J]. Clin Orthop Relat Res, 2001(391 Suppl):S362-S369.
[11] Borem R, Madeline A, Bowman M , et al. Differential effector response of amnion- and adipose-derived mesenchymal stem cells to inflammation; implica-tions for intradiscal therapy[J]. J Orthop Res, 2019,37(11):2445-2456.
doi: 10.1002/jor.24412 pmid: 31287173
[12] Xu LL, Liu YM, Sun YX , et al. Tissue source dete-rmines the differentiation potentials of mesenchymal stem cells: a comparative study of human mesen-chymal stem cells from bone marrow and adipose tissue[J]. Stem Cell Res Ther, 2017,8(1):275.
doi: 10.1186/s13287-017-0716-x pmid: 29208029
[13] Bousnaki M, Bakopoulou A, Papadogianni D , et al. Fibro/chondrogenic differentiation of dental stem cells into chitosan/alginate scaffolds towards temporomandibular joint disc regeneration[J]. J Mater Sci Mater Med, 2018,29(7):97.
doi: 10.1007/s10856-018-6109-6 pmid: 29946796
[14] Yao L, Flynn N . Dental pulp stem cell-derived chondrogenic cells demonstrate differential cell motility in type Ⅰ and type Ⅱ collagen hydrogels[J]. Spine J, 2018,18(6):1070-1080.
doi: 10.1016/j.spinee.2018.02.007 pmid: 29452287
[15] Liang Y, Idrees E, Szojka ARA , et al. Chondrogenic differentiation of synovial fluid mesenchymal stem cells on human meniscus-derived decellularized matrix requires exogenous growth factors[J]. Acta Biomater, 2018,80:131-143.
doi: 10.1016/j.actbio.2018.09.038 pmid: 30267878
[16] Li Y, Tian AY, Ophene J , et al. TGF-β stimulates endochondral differentiation after denervation[J]. Int J Med Sci, 2017,14(4):382-389.
doi: 10.7150/ijms.17364 pmid: 28553171
[17] Zhou Q, Li BJ, Zhao JL , et al. IGF-I induces adipose derived mesenchymal cell chondrogenic differentia-tion in vitro and enhances chondrogenesis in vivo[J]. In Vitro Cell Dev Biol Anim, 2016,52(3):356-364.
[18] Zhang YD, Zhao SC, Zhu ZS , et al. Cx43- and smad-mediated TGF-β/BMP signaling pathway promotes cartilage differentiation of bone marrow mesenchymal stem cells and inhibits osteoblast differentiation[J]. Cell Physiol Biochem, 2017,42(4):1277-1293.
doi: 10.1159/000478957 pmid: 28697500
[19] Liu JC, Liu X, Zhou GD , et al. Conditioned medium from chondrocyte/scaffold constructs induced chon-drogenic differentiation of bone marrow stromal cells[J]. Anat Rec (Hoboken), 2012,295(7):1109-1116.
doi: 10.1002/ar.22500 pmid: 22644958
[20] Tuli R, Tuli S, Nandi S , et al. Transforming growth factor-β-mediated chondrogenesis of human me-senchymal progenitor cells involves N-cadherin and mitogen-activated protein kinase and Wnt signaling cross-talk[J]. J Biol Chem, 2003,278(42):41227-41236.
doi: 10.1074/jbc.M305312200 pmid: 12893825
[21] Grier WK, Tiffany AS, Ramsey MD , et al. Incor-porating β-cyclodextrin into collagen scaffolds to sequester growth factors and modulate mesenchymal stem cell activity[J]. Acta Biomater, 2018,76:116-125.
doi: 10.1016/j.actbio.2018.06.033 pmid: 29944975
[22] Zhai CJ, Zhang X, Chen J , et al. The effect of carti-lage extracellular matrix particle size on the chondro-genic differentiation of bone marrow mesenchymal stem cells[J]. Regen Med, 2019,14(7):663-680.
doi: 10.2217/rme-2018-0082 pmid: 31313645
[23] Zhou M, Lozano N, Wychowaniec JK , et al. Graphene oxide: a growth factor delivery carrier to enhance chondrogenic differentiation of human mesenchymal stem cells in 3D hydrogels[J]. Acta Biomater, 2019,96:271-280.
doi: 10.1016/j.actbio.2019.07.027 pmid: 31325577
[24] Haas AR, Tuan RS . Chondrogenic differentiation of murine C3H10T1/2 multipotential mesenchymal cells: Ⅱ. Stimulation by bone morphogenetic pro-tein-2 requires modulation of N-cadherin expression and function[J]. Differentiation, 1999,64(2):77-89.
doi: 10.1046/j.1432-0436.1999.6420077.x pmid: 10234805
[25] Lee SH, Shin H . Matrices and scaffolds for delivery of bioactive molecules in bone and cartilage tissue engineering[J]. Adv Drug Deliv Rev, 2007,59(4/5):339-359.
doi: 10.1016/j.addr.2007.03.016 pmid: 17499384
[26] Zhao XX, An XL, Zhu XC , et al. Inhibiting trans-forming growth factor-β signaling regulates in vitro maintenance and differentiation of bovine bone marrow mesenchymal stem cells[J]. J Exp Zool B Mol Dev Evol, 2018,330(8):406-416.
doi: 10.1002/jez.b.22836 pmid: 30460778
[27] Zhang L, Su P, Xu C , et al. Chondrogenic differentia-tion of human mesenchymal stem cells: a com-parison between micromass and pellet culture systems[J]. Biotechnol Lett, 2010,32(9):1339-1346.
doi: 10.1007/s10529-010-0293-x pmid: 20464452
[28] Finger AR, Sargent CY, Dulaney KO , et al. Differential effects on messenger ribonucleic acid expression by bone marrow-derived human mesenchymal stem cells seeded in agarose constructs due to ramped and steady applications of cyclic hydrostatic pressure[J]. Tissue Eng, 2007,13(6):1151-1158.
doi: 10.1089/ten.2006.0290 pmid: 17518710
[29] Hennig T, Lorenz H, Thiel A , et al. Reduced chon-drogenic potential of adipose tissue derived stromal cells correlates with an altered TGFβ receptor and BMP profile and is overcome by BMP-6[J]. J Cell Physiol, 2007,211(3):682-691.
doi: 10.1002/jcp.20977 pmid: 17238135
[30] Fang DP, Jin P, Huang QX , et al. Platelet-rich plasma promotes the regeneration of cartilage engineered by mesenchymal stem cells and collagen hydrogel via the TGF-β/SMAD signaling pathway[J]. J Cell Phy-siol, 2019. doi: 10.1002/jcp.28211.
[31] 周晓旭, 彭俊, 胡海 , 等. TGF-β3, HA, PTHrP对人脐带间充质干细胞成软骨分化的影响[J]. 中国比较医学杂志, 2019,29(10):26-32.
Zhou XX, Peng J, Hu H , et al. Effects of transfor-ming growth factor β3, hyaluronic acid, and parathy-roid hormone-related protein on chondrogenic diffe-rentiation of human umbilical cord mesenchymal stem cells[J]. Chin J Comp Med, 2019,29(10):26-32.
[32] Renner JN, Kim Y, Liu JC . Bone morphogenetic protein-derived peptide promotes chondrogenic differentiation of human mesenchymal stem cells[J]. Tissue Eng Part A, 2012,18(23/24):2581-2589.
doi: 10.1089/ten.TEA.2011.0400 pmid: 22765926
[33] Lee PT, Li WJ . Chondrogenesis of embryonic stem cell-derived mesenchymal stem cells induced by TGFβ1 and BMP7 through increased TGFβ receptor expression and endogenous TGFβ1 production[J]. J Cell Biochem, 2017,118(1):172-181.
doi: 10.1002/jcb.25623 pmid: 27292615
[34] Goessler UR, Bugert P, Bieback K , et al. In-vitro analysis of the expression of TGFβ-superfamily-members duringchondrogenic differentiation of me-senchymal stem cells and chondrocytes during de-differentiation in cell culture[J]. Cell Mol Biol Lett, 2005,10(2):345-362.
pmid: 16010298
[35] Fu P, Chen S, Ding Z , et al. Mechanical stimulation promotes osteogenic and chondrogenic differentia-tion of synovial mesenchymal stem cells through BMP-2[J]. Int J Clin Exp Med, 2017,10(2):2842-2849.
[36] Sekiya I, Colter DC, Prockop DJ . BMP-6 enhances chondrogenesis in a subpopulation of human marrow stromal cells[J]. Biochem Biophys Res Commun, 2001,284(2):411-418.
doi: 10.1006/bbrc.2001.4898 pmid: 11394894
[37] 常晓朋, 陈涛, 赵寅 , 等. 骨形态发生蛋白2和转化生长因子β2协同促进骨髓间充质干细胞成骨分化[J]. 中国组织工程研究, 2019,23(1):1-6.
Chang XP, Chen T, Zhao Y , et al. Synergistic effect of bone morphogenetic protein 2 and transforming growth factor β2 on osteogenic differentiation of bone marrow mesenchymal stem cells[J]. Chin J Tissue Eng Res, 2019,23(1):1-6.
[38] Majumdar MK, Wang E, Morris EA . BMP-2 and BMP-9 promotes chondrogenic differentiation of human multipotential mesenchymal cells and over-comes the inhibitory effect of IL-1[J]. J Cell Physiol, 2001,189(3):275-284.
doi: 10.1002/jcp.10025 pmid: 11748585
[39] Freyria AM, Mallein-Gerin F . Chondrocytes or adult stem cells for cartilage repair: the indisputable role of growth factors[J]. Injury, 2012,43(3):259-265.
doi: 10.1016/j.injury.2011.05.035 pmid: 21696723
[40] Lee TH, Kim WT, Ryu CJ , et al. Optimization of treatment with recombinant FGF-2 for proliferation and differentiation of human dental stem cells, me-senchymal stem cells, and osteoblasts[J]. Biochem Cell Biol, 2015,93(4):298-305.
doi: 10.1139/bcb-2014-0140 pmid: 25789782
[41] Zhang W, Green C, Stott NS . Bone morphogenetic protein-2 modulation of chondrogenic differentiation in vitro involves gap junction-mediated intercellular communication[J]. J Cell Physiol, 2002,193(2):233-243.
doi: 10.1002/jcp.10168 pmid: 12385001
[42] Endo K, Fujita N, Nakagawa T , et al. Effect of fibro-blast growth factor-2 and serum on canine mesenchymal stem cell chondrogenesis[J]. Tissue Eng Part A, 2019,25(11/12):901-910.
doi: 10.1089/ten.TEA.2018.0177 pmid: 30319056
[43] Solchaga LA, Penick K, Goldberg VM , et al. Fibro-blast growth factor-2 enhances proliferation and delays loss of chondrogenic potential in human adult bone-marrow-derived mesenchymal stem cells[J]. Tissue Eng Part A, 2010,16(3):1009-1019.
doi: 10.1089/ten.TEA.2009.0100 pmid: 19842915
[44] Manning WK, Bonner WM Jr . Isolation and culture of chondrocytes from human adult articular cartilage[J]. Arthritis Rheum, 1967,10(3):235-239.
doi: 10.1002/art.1780100309 pmid: 4291108
[45] Ito T, Sawada R, Fujiwara Y , et al. FGF-2 increases osteogenic and chondrogenic differentiation poten-tials of human mesenchymal stem cells by inactiva-tion of TGF-β signaling[J]. Cytotechnology, 2008,56(1):1-7.
doi: 10.1007/s10616-007-9092-1 pmid: 19002835
[46] Jiang XR, Huang BT, Yang HY , et al. TGF-β1 is involved in vitamin D-induced chondrogenic diffe-rentiation of bone marrow-derived mesenchymal stem cells by regulating the ERK/JNK pathway[J]. Cell Physiol Biochem, 2017,42(6):2230-2241.
doi: 10.1159/000479997 pmid: 28817810
[47] Li YY, Lam KL, Chen AD , et al. Collagen microe-ncapsulation recapitulates mesenchymal condensa-tion and potentiates chondrogenesis of human me-senchymal stem cell—a matrix-driven in vitro model of early skeletogenesis[J]. Biomaterials, 2019,213:119210.
doi: 10.1016/j.biomaterials.2019.05.021 pmid: 31132645
[48] Derfoul A, Perkins GL, Hall DJ , et al. Glucocorticoids promote chondrogenic differentiation of adult human mesenchymal stem cells by enhancing expression of cartilage extracellular matrix genes[J]. Stem Cells, 2006,24(6):1487-1495.
doi: 10.1634/stemcells.2005-0415 pmid: 16469821
[49] Indrawattana N, Chen G, Tadokoro M , et al. Growth factor combination for chondrogenic induction from human mesenchymal stem cell[J]. Biochem Biophys Res Commun, 2004,320(3):914-919.
doi: 10.1016/j.bbrc.2004.06.029 pmid: 15240135
[50] Fukumoto T, Sperling JW, Sanyal A , et al. Combined effects of insulin-like growth factor-1 and transfor-ming growth factor-β on periosteal mesenchymal cells during chondrogenesis in vitro[J]. Osteoarthritis Cartilage, 2003,11(1):55-64.
doi: 10.1053/joca.2002.0869 pmid: 12505488
[51] Hara ES, Ono M, Pham HT , et al. Fluocinolone acetonide is a potent synergistic factor of TGF-β3-associated chondrogenesis of bone marrow-derived mesenchymal stem cells for articular surface re-generation[J]. J Bone Miner Res, 2015,30(9):1585-1596.
doi: 10.1002/jbmr.2502 pmid: 25753754
[1] 李佩桐,时彬冕,许春梅,谢旭东,王骏. Gli1阳性间充质干细胞在牙及牙周组织中的分布及作用[J]. 国际口腔医学杂志, 2023, 50(1): 37-42.
[2] 周灿,曾倩,韦曦. 浓缩生长因子在活髓保存治疗中的应用前景[J]. 国际口腔医学杂志, 2022, 49(6): 684-689.
[3] 熊梦琳,吴龙,马丽,赵今. 转化生长因子-β2促进牙髓干细胞增殖和分化的作用研究[J]. 国际口腔医学杂志, 2021, 48(6): 635-639.
[4] 施培磊,于晨浩,谢旭东,吴亚菲,王骏. 牙源性间充质干细胞应用于牙周组织缺损修复的研究进展[J]. 国际口腔医学杂志, 2021, 48(6): 690-695.
[5] 刘娟,陈斌,闫福华. 富血小板血浆和浓缩生长因子对人牙周膜细胞增殖和成骨分化影响的研究[J]. 国际口腔医学杂志, 2021, 48(5): 520-527.
[6] 巩靖蕾,黄艳梅,王军. 多相支架在牙周再生领域的研究进展[J]. 国际口腔医学杂志, 2021, 48(5): 563-569.
[7] 邓诗勇,宫苹,谭震. 脑和肌肉芳香烃受体核转运样蛋白1基因调控口腔及全身骨代谢的作用[J]. 国际口腔医学杂志, 2021, 48(2): 198-204.
[8] 陈野, 周丰, 邬琼辉, 车会凌, 李佳璇, 申佳琪, 罗恩. 脂联素对骨髓间充质干细胞的作用及其调控机制[J]. 国际口腔医学杂志, 2021, 48(1): 58-63.
[9] 吕辉,王华,孙雯. 辅助性T细胞17与牙周炎骨免疫[J]. 国际口腔医学杂志, 2020, 47(6): 661-668.
[10] 杨叶青,陈明,吴补领. 环状非编码RNA在间充质干细胞成骨向分化中作用的研究进展[J]. 国际口腔医学杂志, 2020, 47(3): 257-262.
[11] 刘俊圻,陈艺尹,杨文宾. RNA腺嘌呤6-甲基化修饰调控骨髓间充质干细胞成骨向分化的研究进展[J]. 国际口腔医学杂志, 2020, 47(3): 263-269.
[12] 吴晓楠,马宁,侯建霞. 不同干细胞来源外泌体在牙周再生领域的研究进展[J]. 国际口腔医学杂志, 2020, 47(2): 146-151.
[13] 魏中武,黄谢山,陈灼庚. 浓缩生长因子在口腔临床中的应用及研究进展[J]. 国际口腔医学杂志, 2020, 47(2): 235-243.
[14] 王小萌,王晓,史册,孙宏晨,黄洋. 骨形态发生蛋白信号通路及其交叉对话对下颌骨发育的影响[J]. 国际口腔医学杂志, 2019, 46(3): 258-262.
[15] 杨亚,陈鹏,戴红卫,张林. 大鼠正畸牙移动过程中转化生长因子-β/Smad信号通路相关蛋白质在Malassez上皮剩余细胞的表达变化[J]. 国际口腔医学杂志, 2019, 46(3): 270-276.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] 张新春. 桩冠修复与无髓牙的保护[J]. 国际口腔医学杂志, 1999, 26(06): .
[2] 王昆润. 长期单侧鼻呼吸对头颅发育有不利影响[J]. 国际口腔医学杂志, 1999, 26(05): .
[3] 彭国光. 颈淋巴清扫术中颈交感神经干的解剖变异[J]. 国际口腔医学杂志, 1999, 26(05): .
[4] 杨凯. 淋巴化疗的药物运载系统及其应用现状[J]. 国际口腔医学杂志, 1999, 26(05): .
[5] 康非吾. 种植义齿下部结构生物力学研究进展[J]. 国际口腔医学杂志, 1999, 26(05): .
[6] 柴枫. 可摘局部义齿用Co-Cr合金的激光焊接[J]. 国际口腔医学杂志, 1999, 26(04): .
[7] 孟姝,吴亚菲,杨禾. 伴放线放线杆菌产生的细胞致死膨胀毒素及其与牙周病的关系[J]. 国际口腔医学杂志, 2005, 32(06): 458 -460 .
[8] 费晓露,丁一,徐屹. 牙周可疑致病菌对口腔黏膜上皮的粘附和侵入[J]. 国际口腔医学杂志, 2005, 32(06): 452 -454 .
[9] 赵兴福,黄晓晶. 变形链球菌蛋白组学研究进展[J]. 国际口腔医学杂志, 2008, 35(S1): .
[10] 庞莉苹,姚江武. 抛光和上釉对陶瓷表面粗糙度、挠曲强度及磨损性能的影响[J]. 国际口腔医学杂志, 2008, 35(S1): .