细胞因子及软骨工程支架对脂肪源性干细胞成软骨分化的作用、难点及内在机制
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摘要
背景:软骨组织工程是目前的研究热点,它可以克服自体软骨移植损伤与材料来源不足等问题。寻找来源充足且具有强大体外增殖能力和多向分化潜能的干细胞作为软骨种子细胞具有重要的意义。目的:对脂肪源性干细胞的成软骨分化研究进展及目前主要难题等进行综述。方法:在PubMed、万方、CNKI等数据库中以"adipose-derived stem cells/ASCs,chondrocyte,cartilage,cytokine";"脂肪源性干细胞,软骨,细胞因子"为关键词检索2000年至今的文献。广泛查阅近年关于脂肪源性干细胞成软骨分化的实验研究及临床研究,根据文献价值详略地进行整理、综合与分析。结果与结论:(1)脂肪源性干细胞成软骨分化研究主要集中在外源性骨形态发生蛋白、转化生长因子β、胰岛素样生长因子1、生长分化因子5、碱性成纤维细胞生长因子、地塞米松等因子及其相互作用方面;(2)软骨诱导支架不仅能促进脂肪源性干细胞诱导分化、细胞增殖,还能弥补分泌细胞外基质不足,加速了用于移植的组织块产生;(3)目前脂肪源性干细胞诱导成软骨分化主要集中在探索性研究阶段,需要进一步的机制研究及临床转化研究将其应用于临床治疗中。
BACKGROUND: Cartilage tissue engineering is currently a research hotspot, which can overcome the problems of autologous cartilage injury and insufficient material sources encountered in autologous cartilage transplantation.It is of great significance to seek sufficient sources of stem cells with strong in vitro proliferation ability and multi-directional differentiation potential as cartilage seed cells. OBJECTIVE: To review the progress of chondrogenic differentiation of adipose-derived stem cells as well as the main existing problems. METHODS: We extensively reviewed experimental research and clinical trial regarding the chondrogenic differentiation of adipose-derived stem cells in the PubMed, WanFang, and CNKI from 2000 to present. The keywords were "adipose-derived stem cells/ASCs, chondrocyte, cartilage, cytokine" in English and Chinese, respectively. All the retrieved literatures were synthesized and analyzed in detail or concisely according to the literature reference value. RESULTS AND CONCLUSION: Existing studies regarding the chondrogenic differentiation of adipose-derived stem cells mainly focus on exogenous cytokines, including bone morphogenetic protein, transforming growth factor β, insulin-like growth factor 1, growth differentiation factor 5, basic fibroblast growth factor, and dexamethasone, as well as their interactions. Cartilage tissue-engineered scaffolds cannot only promote the differentiation and proliferation of adipose-derived stem cells, but also compensate for the lack of extracellular matrix and accelerate the production of tissue blocks for transplantation. At present, to induce the chondrogenic differentiation of adipose-derived stem cells is mainly in exploratory stage, and further explorations on relevant mechanism are needed to introduce the chondrogenic differentiation of adipose-derived stem cells into the clinical use.
BACKGROUND: Cartilage tissue engineering is currently a research hotspot, which can overcome the problems of autologous cartilage injury and insufficient material sources encountered in autologous cartilage transplantation.It is of great significance to seek sufficient sources of stem cells with strong in vitro proliferation ability and multi-directional differentiation potential as cartilage seed cells. OBJECTIVE: To review the progress of chondrogenic differentiation of adipose-derived stem cells as well as the main existing problems. METHODS: We extensively reviewed experimental research and clinical trial regarding the chondrogenic differentiation of adipose-derived stem cells in the PubMed, WanFang, and CNKI from 2000 to present. The keywords were "adipose-derived stem cells/ASCs, chondrocyte, cartilage, cytokine" in English and Chinese, respectively. All the retrieved literatures were synthesized and analyzed in detail or concisely according to the literature reference value. RESULTS AND CONCLUSION: Existing studies regarding the chondrogenic differentiation of adipose-derived stem cells mainly focus on exogenous cytokines, including bone morphogenetic protein, transforming growth factor β, insulin-like growth factor 1, growth differentiation factor 5, basic fibroblast growth factor, and dexamethasone, as well as their interactions. Cartilage tissue-engineered scaffolds cannot only promote the differentiation and proliferation of adipose-derived stem cells, but also compensate for the lack of extracellular matrix and accelerate the production of tissue blocks for transplantation. At present, to induce the chondrogenic differentiation of adipose-derived stem cells is mainly in exploratory stage, and further explorations on relevant mechanism are needed to introduce the chondrogenic differentiation of adipose-derived stem cells into the clinical use.
引文
[1]Hildner F, Albrecht C, Gabriel C, et al. State of the art and future perspectives of articular cartilage regeneration:a focus on adipose-derived stem cells and platelet-derived products.J Tissue Eng Regen Med. 2011;5(4):e36-51.
[2]Diekman BO, Estes BT, Guilak F.The effects of BMP6overexpression on adipose stem cell chondrogenesis:Interactions with dexamethasone and exogenous growth factors.J Biomed Mater Res A. 2010;93(3):994-1003.
[3]Mardani M, Hashemibeni B, Ansar MM, et al. Comparison between Chondrogenic Markers of Differentiated Chondrocytes from Adipose Derived Stem Cells and Articular Chondrocytes In Vitro.Iran J Basic Med Sci. 2013;16(6):763-773.
[4]Ude CC, Chen HC, Norhamdan MY, et al. The evaluation of cartilage differentiations using transforming growth factor beta3alone and with combination of bone morphogenetic protein-6on adult stem cells.Cell Tissue Bank. 2017;18(3):355-367.
[5]Jungmann PM, Mehlhorn AT, Schmal H, et al.Nanomechanics of human adipose-derived stem cells:small GTPases impact chondrogenic differentiation.Tissue Eng Part A. 2012;18(9-10):1035-1044.
[6]An C, Cheng Y, Yuan Q, et al. IGF-1 and BMP-2 induces differentiation of adipose-derived mesenchymal stem cells into chondrocytes-like cells.Ann Biomed Eng. 2010;38(4):1647-1654.
[7]Goh BS, Che Omar SN, Ubaidah MA, et al. Chondrogenesis of human adipose derived stem cells for future microtia repair using co-culture technique.Acta Otolaryngol. 2017;137(4):432-441.
[8]Song X, Hong C, Zheng Q, et al. Differentiation potential of rabbit CD90-positive cells sorted from adipose-derived stem cells in vitro.In Vitro Cell Dev Biol Anim. 2017;53(1):77-82.
[9]Hildner F, Concaro S, Peterbauer A, et al. Human adipose-derived stem cells contribute to chondrogenesis in coculture with human articular chondrocytes.Tissue Eng Part A.2009;15(12):3961-3969.
[10]Estes BT, Diekman BO, Gimble JM, et al. Isolation of adipose-derived stem cells and their induction to a chondrogenic phenotype.Nat Protoc. 2010;5(7):1294-1311.
[11]Ansar MM, Esfandiariy E, Mardani M, et al. A comparative study of aggrecan synthesis between natural articular chondrocytes and differentiated chondrocytes from adipose derived stem cells in 3D culture.Adv Biomed Res. 2012;1:24.
[12]张传辉,李建军,杨军.调控脂肪间充质干细胞成软骨分化基因Sox-9和低氧诱导因子1α的表达[J].中国组织工程研究, 2016,20(45):6766-6773.
[13]Chiou M, Xu Y, Longaker MT.Mitogenic and chondrogenic effects of fibroblast growth factor-2 in adipose-derived mesenchymal cells.BiochemBiophys Res Commun. 2006;343(2):644-652.
[14]Quarto N, Longaker MT.FGF-2 inhibits osteogenesis in mouse adipose tissue-derived stromal cells and sustains their proliferative and osteogenic potential state.Tissue Eng. 2006;12(6):1405-1418.
[15]Lee JM, Im GI.SOX trio-co-transduced adipose stem cells in fibrin gel to enhance cartilage repair and delay the progression of osteoarthritis in the rat.Biomaterials. 2012;33(7):2016-2024.
[16]López-Ruiz E, Perán M, Cobo-Molinos J, et al. Chondrocytes extract from patients with osteoarthritis induces chondrogenesis in infrapatellar fat pad-derived stem cells.Osteoarthritis Cartilage. 2013;21(1):246-258.
[17]Estes BT, Wu AW, Storms RW, et al. Extended passaging, but not aldehyde dehydrogenase activity, increases the chondrogenic potential of human adipose-derived adult stem cells.J Cell Physiol. 2006;209(3):987-995.
[18]Estes BT, Wu AW, Guilak F.Potent induction of chondrocytic differentiation of human adipose-derived adult stem cells by bone morphogenetic protein 6.Arthritis Rheum. 2006;54(4):1222-1232.
[19]Ogawa R, Orgill DP, Murphy GF, et al. Hydrostatic pressure-driven three-dimensional cartilage induction using human adipose-derived stem cells and collagen gels.Tissue Eng Part A. 2015;21(1-2):257-266.
[20]Bonakdar S, Mahmoudi M, Montazeri L, et al. Cell-Imprinted Substrates Modulate Differentiation, Redifferentiation, and Transdifferentiation.ACS Appl Mater Interfaces. 2016;8(22):13777-13784.
[21]赵明璨,刘畅.脂肪干细胞在软骨组织工程中的研究进展[J].中国生物医学工程学报,2014,33(4):475-481.
[22]Zaragosi LE, Billon N, Ailhaud G, et al. Nucleofection is a valuable transfection method for transient and stable transgene expression in adipose tissue-derived stem cells.Stem Cells. 2007;25(3):790-797.
[23]Grimsrud CD, Romano PR, D'Souza M, et al. BMP signaling stimulates chondrocyte maturation and the expression of Indian hedgehog.J Orthop Res. 2001;19(1):18-25.
[24]Jin XB, Sun YS, Zhang K, et al. Tissue engineered cartilage from hTGF beta2 transduced human adipose derived stem cells seeded in PLGA/alginate compound in vitro and in vivo.J Biomed Mater Res A. 2008;86(4):1077-1087.
[25]Diekman BO, Rowland CR, Lennon DP, et al.Chondrogenesis of adult stem cells from adipose tissue and bone marrow:induction by growth factors and cartilage-derived matrix.Tissue Eng Part A. 2010;16(2):523-533.
[26]Lu CH, Lin KJ, Chiu HY, et al. Improved chondrogenesis and engineered cartilage formation from TGF-β3-expressing adipose-derived stem cells cultured in the rotating-shaft bioreactor.Tissue Eng Part A. 2012;18(19-20):2114-2124.
[27]Kawai M, Rosen CJ.The IGF-I regulatory system and its impact on skeletal and energy homeostasis.J Cell Biochem.2010;111(1):14-19.
[28]Liu Z, Jia C, Han C.Experimental study on chondrogenic differentiation of rabbit adipose-derived stem cells treated with growth differentiation factor 5. ZhongguoXiu Fu Chong Jian Wai KeZaZhi. 2009;23(4):483-489.
[29]Feng G, Wan Y, Balian G, et al. Adenovirus-mediated expression of growth and differentiation factor-5 promotes chondrogenesis of adipose stem cells.Growth Factors.2008;26(3):132-142.
[30]Tian H, Stogiannidis I.Up-regulation of cartilage oligomeric matrix protein gene expression by insulin-like growth factor-I revealed by real-time reverse transcription-polymerase chain reaction. ActaBiochimBiophys Sin(Shanghai). 2006;38(10):677-682.
[31]Sakimura K, Matsumoto T, Miyamoto C, et al. Effects of insulin-like growth factor I on transforming growth factor beta1induced chondrogenesis of synovium-derived mesenchymal stem cells cultured in a polyglycolic acid scaffold. Cells Tissues Organs. 2006;183(2):55-61.
[32]Chen WJ, Jingushi S, Aoyama I, et al. Effects of FGF-2 on metaphyseal fracture repair in rabbit tibiae.J Bone Miner Metab. 2004;22(4):303-309.
[33]Varkey M, Kucharski C, Haque T, et al. In vitro osteogenic response of rat bone marrow cells to bFGF and BMP-2treatments.Clin Orthop Relat Res. 2006;443:113-123.
[34]Liu Y, Titus L, Barghouthi M, et al. Glucocorticoid regulation of human BMP-6 transcription.Bone. 2004;35(3):673-681.
[35]Li J, Zhao Q, Wang E, et al. Dynamic compression of rabbit adipose-derived stem cells transfected with insulin-like growth factor 1 in chitosan/gelatin scaffolds induces chondrogenesis and matrix biosynthesis.J Cell Physiol. 2012;227(5):2003-2012.
[36]Madry H, Orth P, Kaul G, et al. Acceleration of articular cartilage repair by combined gene transfer of human insulin-like growth factor I and fibroblast growth factor-2 in vivo.Arch Orthop Trauma Surg. 2010;130(10):1311-1322.
[37]甘凤英,唐琛,叶德富,等.生长因子联合诱导大鼠间充质干细胞向软骨分化的实验研究[J].中华风湿病学杂志, 2007,11(11):658-661.
[38]Hennig T, Lorenz H, Thiel A, et al. Reduced chondrogenic potential of adipose tissue derived stromal cells correlates with an altered TGFbeta receptor and BMP profile and is overcome by BMP-6.J Cell Physiol. 2007;211(3):682-691.
[39]Wei Y, Hu Y, Lv R, et al. Regulation of adipose-derived adult stem cells differentiating into chondrocytes with the use of rhBMP-2.Cytotherapy. 2006;8(6):570-579.
[40]Luo S, Shi Q, Zha Z, et al. Inactivation of Wnt/β-catenin signaling in human adipose-derived stem cells is necessary for chondrogenic differentiation and maintenance.Biomed Pharmacother. 2013;67(8):819-824.
[41]Esfandiari E, Roshankhah S, Mardani M, et al. The effect of high frequency electric field on enhancement of chondrogenesis in human adipose-derived stem cells.Iran J Basic Med Sci. 2014;17(8):571-576.
[42]Cai Z, Pan B, Jiang H, et al. Chondrogenesis of Human Adipose-Derived Stem Cells by In Vivo Co-graft with Auricular Chondrocytes from Microtia.Aesthetic Plast Surg. 2015;39(3):431-439.
[43]Lee JS, Im GI.Influence of chondrocytes on the chondrogenic differentiation of adipose stem cells.Tissue Eng Part A. 2010;16(12):3569-3577.
[44]Mahmoudifar N, Doran PM.Extent of cell differentiation and capacity for cartilage synthesis in human adult adipose-derived stem cells:comparison with fetal chondrocytes. BiotechnolBioeng. 2010;107(2):393-401.
[45]Yeh HY, Lin TY, Lin CH, et al. Neocartilage formation from mesenchymal stem cells grown in type II collagen-hyaluronan composite scaffolds.Differentiation. 2013;86(4-5):171-183.
[46]Yeon B, Park MH, Moon HJ, et al. 3D culture of adipose-tissue-derived stem cells mainly leads to chondrogenesis in poly(ethylene glycol)-poly(L-alanine)diblock copolymer thermogel.Biomacromolecules. 2013;14(9):3256-3266.
[47]Cheng NC, Estes BT, Young TH, et al. Genipin-crosslinked cartilage-derived matrix as a scaffold for human adipose-derived stem cell chondrogenesis.Tissue Eng Part A.2013;19(3-4):484-496.
[48]Mizuno S, Allemann F, Glowacki J.Effects of medium perfusion on matrix production by bovine chondrocytes in three-dimensional collagen sponges.J Biomed Mater Res.2001;56(3):368-375.
[49]Wang ZJ, An RZ, Zhao JY, et al. Repair of articular cartilage defects by tissue-engineered cartilage constructed with adipose-derived stem cells and acellular cartilaginous matrix in rabbits.Genet Mol Res. 2014;13(2):4599-4606.
[50]Kim HJ, Park SH, Durham J, et al. In vitro chondrogenic differentiation of human adipose-derived stem cells with silk scaffolds.J Tissue Eng. 2012;3(1):2041731412466405.
[51]Yoon HH, Bhang SH, Shin JY, et al. Enhanced cartilage formation via three-dimensional cell engineering of human adipose-derived stem cells.Tissue Eng Part A. 2012;18(19-20):1949-1956.
[52]Wang J, Zhou Q, Deng LF, et al. In vitro and in vivo study of chondrogenesis on the hybrid scaffold from fibrin modified PLGA and adipose-derived stem cells. Xi Bao Yu FenZi Mian Yi Xue ZaZhi. 2010;26(8):758-760.
[2]Diekman BO, Estes BT, Guilak F.The effects of BMP6overexpression on adipose stem cell chondrogenesis:Interactions with dexamethasone and exogenous growth factors.J Biomed Mater Res A. 2010;93(3):994-1003.
[3]Mardani M, Hashemibeni B, Ansar MM, et al. Comparison between Chondrogenic Markers of Differentiated Chondrocytes from Adipose Derived Stem Cells and Articular Chondrocytes In Vitro.Iran J Basic Med Sci. 2013;16(6):763-773.
[4]Ude CC, Chen HC, Norhamdan MY, et al. The evaluation of cartilage differentiations using transforming growth factor beta3alone and with combination of bone morphogenetic protein-6on adult stem cells.Cell Tissue Bank. 2017;18(3):355-367.
[5]Jungmann PM, Mehlhorn AT, Schmal H, et al.Nanomechanics of human adipose-derived stem cells:small GTPases impact chondrogenic differentiation.Tissue Eng Part A. 2012;18(9-10):1035-1044.
[6]An C, Cheng Y, Yuan Q, et al. IGF-1 and BMP-2 induces differentiation of adipose-derived mesenchymal stem cells into chondrocytes-like cells.Ann Biomed Eng. 2010;38(4):1647-1654.
[7]Goh BS, Che Omar SN, Ubaidah MA, et al. Chondrogenesis of human adipose derived stem cells for future microtia repair using co-culture technique.Acta Otolaryngol. 2017;137(4):432-441.
[8]Song X, Hong C, Zheng Q, et al. Differentiation potential of rabbit CD90-positive cells sorted from adipose-derived stem cells in vitro.In Vitro Cell Dev Biol Anim. 2017;53(1):77-82.
[9]Hildner F, Concaro S, Peterbauer A, et al. Human adipose-derived stem cells contribute to chondrogenesis in coculture with human articular chondrocytes.Tissue Eng Part A.2009;15(12):3961-3969.
[10]Estes BT, Diekman BO, Gimble JM, et al. Isolation of adipose-derived stem cells and their induction to a chondrogenic phenotype.Nat Protoc. 2010;5(7):1294-1311.
[11]Ansar MM, Esfandiariy E, Mardani M, et al. A comparative study of aggrecan synthesis between natural articular chondrocytes and differentiated chondrocytes from adipose derived stem cells in 3D culture.Adv Biomed Res. 2012;1:24.
[12]张传辉,李建军,杨军.调控脂肪间充质干细胞成软骨分化基因Sox-9和低氧诱导因子1α的表达[J].中国组织工程研究, 2016,20(45):6766-6773.
[13]Chiou M, Xu Y, Longaker MT.Mitogenic and chondrogenic effects of fibroblast growth factor-2 in adipose-derived mesenchymal cells.BiochemBiophys Res Commun. 2006;343(2):644-652.
[14]Quarto N, Longaker MT.FGF-2 inhibits osteogenesis in mouse adipose tissue-derived stromal cells and sustains their proliferative and osteogenic potential state.Tissue Eng. 2006;12(6):1405-1418.
[15]Lee JM, Im GI.SOX trio-co-transduced adipose stem cells in fibrin gel to enhance cartilage repair and delay the progression of osteoarthritis in the rat.Biomaterials. 2012;33(7):2016-2024.
[16]López-Ruiz E, Perán M, Cobo-Molinos J, et al. Chondrocytes extract from patients with osteoarthritis induces chondrogenesis in infrapatellar fat pad-derived stem cells.Osteoarthritis Cartilage. 2013;21(1):246-258.
[17]Estes BT, Wu AW, Storms RW, et al. Extended passaging, but not aldehyde dehydrogenase activity, increases the chondrogenic potential of human adipose-derived adult stem cells.J Cell Physiol. 2006;209(3):987-995.
[18]Estes BT, Wu AW, Guilak F.Potent induction of chondrocytic differentiation of human adipose-derived adult stem cells by bone morphogenetic protein 6.Arthritis Rheum. 2006;54(4):1222-1232.
[19]Ogawa R, Orgill DP, Murphy GF, et al. Hydrostatic pressure-driven three-dimensional cartilage induction using human adipose-derived stem cells and collagen gels.Tissue Eng Part A. 2015;21(1-2):257-266.
[20]Bonakdar S, Mahmoudi M, Montazeri L, et al. Cell-Imprinted Substrates Modulate Differentiation, Redifferentiation, and Transdifferentiation.ACS Appl Mater Interfaces. 2016;8(22):13777-13784.
[21]赵明璨,刘畅.脂肪干细胞在软骨组织工程中的研究进展[J].中国生物医学工程学报,2014,33(4):475-481.
[22]Zaragosi LE, Billon N, Ailhaud G, et al. Nucleofection is a valuable transfection method for transient and stable transgene expression in adipose tissue-derived stem cells.Stem Cells. 2007;25(3):790-797.
[23]Grimsrud CD, Romano PR, D'Souza M, et al. BMP signaling stimulates chondrocyte maturation and the expression of Indian hedgehog.J Orthop Res. 2001;19(1):18-25.
[24]Jin XB, Sun YS, Zhang K, et al. Tissue engineered cartilage from hTGF beta2 transduced human adipose derived stem cells seeded in PLGA/alginate compound in vitro and in vivo.J Biomed Mater Res A. 2008;86(4):1077-1087.
[25]Diekman BO, Rowland CR, Lennon DP, et al.Chondrogenesis of adult stem cells from adipose tissue and bone marrow:induction by growth factors and cartilage-derived matrix.Tissue Eng Part A. 2010;16(2):523-533.
[26]Lu CH, Lin KJ, Chiu HY, et al. Improved chondrogenesis and engineered cartilage formation from TGF-β3-expressing adipose-derived stem cells cultured in the rotating-shaft bioreactor.Tissue Eng Part A. 2012;18(19-20):2114-2124.
[27]Kawai M, Rosen CJ.The IGF-I regulatory system and its impact on skeletal and energy homeostasis.J Cell Biochem.2010;111(1):14-19.
[28]Liu Z, Jia C, Han C.Experimental study on chondrogenic differentiation of rabbit adipose-derived stem cells treated with growth differentiation factor 5. ZhongguoXiu Fu Chong Jian Wai KeZaZhi. 2009;23(4):483-489.
[29]Feng G, Wan Y, Balian G, et al. Adenovirus-mediated expression of growth and differentiation factor-5 promotes chondrogenesis of adipose stem cells.Growth Factors.2008;26(3):132-142.
[30]Tian H, Stogiannidis I.Up-regulation of cartilage oligomeric matrix protein gene expression by insulin-like growth factor-I revealed by real-time reverse transcription-polymerase chain reaction. ActaBiochimBiophys Sin(Shanghai). 2006;38(10):677-682.
[31]Sakimura K, Matsumoto T, Miyamoto C, et al. Effects of insulin-like growth factor I on transforming growth factor beta1induced chondrogenesis of synovium-derived mesenchymal stem cells cultured in a polyglycolic acid scaffold. Cells Tissues Organs. 2006;183(2):55-61.
[32]Chen WJ, Jingushi S, Aoyama I, et al. Effects of FGF-2 on metaphyseal fracture repair in rabbit tibiae.J Bone Miner Metab. 2004;22(4):303-309.
[33]Varkey M, Kucharski C, Haque T, et al. In vitro osteogenic response of rat bone marrow cells to bFGF and BMP-2treatments.Clin Orthop Relat Res. 2006;443:113-123.
[34]Liu Y, Titus L, Barghouthi M, et al. Glucocorticoid regulation of human BMP-6 transcription.Bone. 2004;35(3):673-681.
[35]Li J, Zhao Q, Wang E, et al. Dynamic compression of rabbit adipose-derived stem cells transfected with insulin-like growth factor 1 in chitosan/gelatin scaffolds induces chondrogenesis and matrix biosynthesis.J Cell Physiol. 2012;227(5):2003-2012.
[36]Madry H, Orth P, Kaul G, et al. Acceleration of articular cartilage repair by combined gene transfer of human insulin-like growth factor I and fibroblast growth factor-2 in vivo.Arch Orthop Trauma Surg. 2010;130(10):1311-1322.
[37]甘凤英,唐琛,叶德富,等.生长因子联合诱导大鼠间充质干细胞向软骨分化的实验研究[J].中华风湿病学杂志, 2007,11(11):658-661.
[38]Hennig T, Lorenz H, Thiel A, et al. Reduced chondrogenic potential of adipose tissue derived stromal cells correlates with an altered TGFbeta receptor and BMP profile and is overcome by BMP-6.J Cell Physiol. 2007;211(3):682-691.
[39]Wei Y, Hu Y, Lv R, et al. Regulation of adipose-derived adult stem cells differentiating into chondrocytes with the use of rhBMP-2.Cytotherapy. 2006;8(6):570-579.
[40]Luo S, Shi Q, Zha Z, et al. Inactivation of Wnt/β-catenin signaling in human adipose-derived stem cells is necessary for chondrogenic differentiation and maintenance.Biomed Pharmacother. 2013;67(8):819-824.
[41]Esfandiari E, Roshankhah S, Mardani M, et al. The effect of high frequency electric field on enhancement of chondrogenesis in human adipose-derived stem cells.Iran J Basic Med Sci. 2014;17(8):571-576.
[42]Cai Z, Pan B, Jiang H, et al. Chondrogenesis of Human Adipose-Derived Stem Cells by In Vivo Co-graft with Auricular Chondrocytes from Microtia.Aesthetic Plast Surg. 2015;39(3):431-439.
[43]Lee JS, Im GI.Influence of chondrocytes on the chondrogenic differentiation of adipose stem cells.Tissue Eng Part A. 2010;16(12):3569-3577.
[44]Mahmoudifar N, Doran PM.Extent of cell differentiation and capacity for cartilage synthesis in human adult adipose-derived stem cells:comparison with fetal chondrocytes. BiotechnolBioeng. 2010;107(2):393-401.
[45]Yeh HY, Lin TY, Lin CH, et al. Neocartilage formation from mesenchymal stem cells grown in type II collagen-hyaluronan composite scaffolds.Differentiation. 2013;86(4-5):171-183.
[46]Yeon B, Park MH, Moon HJ, et al. 3D culture of adipose-tissue-derived stem cells mainly leads to chondrogenesis in poly(ethylene glycol)-poly(L-alanine)diblock copolymer thermogel.Biomacromolecules. 2013;14(9):3256-3266.
[47]Cheng NC, Estes BT, Young TH, et al. Genipin-crosslinked cartilage-derived matrix as a scaffold for human adipose-derived stem cell chondrogenesis.Tissue Eng Part A.2013;19(3-4):484-496.
[48]Mizuno S, Allemann F, Glowacki J.Effects of medium perfusion on matrix production by bovine chondrocytes in three-dimensional collagen sponges.J Biomed Mater Res.2001;56(3):368-375.
[49]Wang ZJ, An RZ, Zhao JY, et al. Repair of articular cartilage defects by tissue-engineered cartilage constructed with adipose-derived stem cells and acellular cartilaginous matrix in rabbits.Genet Mol Res. 2014;13(2):4599-4606.
[50]Kim HJ, Park SH, Durham J, et al. In vitro chondrogenic differentiation of human adipose-derived stem cells with silk scaffolds.J Tissue Eng. 2012;3(1):2041731412466405.
[51]Yoon HH, Bhang SH, Shin JY, et al. Enhanced cartilage formation via three-dimensional cell engineering of human adipose-derived stem cells.Tissue Eng Part A. 2012;18(19-20):1949-1956.
[52]Wang J, Zhou Q, Deng LF, et al. In vitro and in vivo study of chondrogenesis on the hybrid scaffold from fibrin modified PLGA and adipose-derived stem cells. Xi Bao Yu FenZi Mian Yi Xue ZaZhi. 2010;26(8):758-760.