3D细胞培养在药物研发中的研究进展
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摘要
3D培养模型的引入是细胞培养技术的一个里程碑,随着新型支架、基质的发明与应用及细胞成像和分析系统的日新月异,三维细胞培养可模拟体内微环境而获得传统2D细胞培养所没有的优势,已在基础研究、干细胞及组织工程等领域崭露头角。本文通过回顾3D细胞培养在药敏实验、药物筛选、药物研发、临床应用中的贡献,从药物效应、药物代谢及药物敏感性着手,枚举3D细胞培养通过改变基因/蛋白质差异表达来进行药物研发,并对其应用趋势、潜在优势和不足作一综述,为基础研究和临床应用提供理论依据。
The introduction of 3D culture models was a milestone in cell culture technology.With the invention and application of new scaffolds and matrices as well as the rapid development of cell imaging and analysis systems,ThreeDimensional Cell Culture(TDCC)could simulate the microenvironment in vivo and gain advantages that traditional 2 D cell culture did not have,which has been emerging in the fields of basic research,stem cells and tissue engineering.In this paper,by reviewing the contributions of 3D cell culture in drug sensitivity experiment,drug screening, drug research and development,and clinical application,starting from drug effect,drug metabolism and drug sensitivity,3D cell culture was enumerated to conduct drug research and development by changing the differential expression of genes/proteins,and its application trend,potential advantages and disadvantages were summarized to provide theoretical basis for basic research and clinical application.
The introduction of 3D culture models was a milestone in cell culture technology.With the invention and application of new scaffolds and matrices as well as the rapid development of cell imaging and analysis systems,ThreeDimensional Cell Culture(TDCC)could simulate the microenvironment in vivo and gain advantages that traditional 2 D cell culture did not have,which has been emerging in the fields of basic research,stem cells and tissue engineering.In this paper,by reviewing the contributions of 3D cell culture in drug sensitivity experiment,drug screening, drug research and development,and clinical application,starting from drug effect,drug metabolism and drug sensitivity,3D cell culture was enumerated to conduct drug research and development by changing the differential expression of genes/proteins,and its application trend,potential advantages and disadvantages were summarized to provide theoretical basis for basic research and clinical application.
引文
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[24]Castillo G,Jiang X.Abstract 5447:Association of the hedgehog signal pathway to Gefitinib sensitivity in a 3D cancer cell lines screening[J].Cancer Research,2015,75(12):5852-5862.
[25]Shoemaker J T,Vukasinovic J.Abstract 4080:Cytochrome P450 enzyme activity is enhanced in hepatocytes grown using a perfused 3D cell culture drug screening system[J].Cancer Research,2017,77(13):4080.
[26]Abefukasawa N,Otsuka K,Aihara A,et al.Novel 3D Liquid Cell Culture Method for Anchorage-independent CellGrowth,CellImagingandAutomatedDrug Screening[J].Scientific Reports,2018,8(1):3627.
[27]Souza A G,Silva I,Camposfernandez E,et al.Comparative Assay of 2D and 3D Cell Culture Models:roliferation,Gene Expression and Anticancer Drug Response.[J].Current Pharmaceutical Design,2018,24(9):17-18.
[28]Han J,Oh S,Hoang HH,et al.Recapitulation of cancer stem cell niches in glioblastoma on 3D microfluidic cell culture devices under gravity-driven perfusion[J].Journal of Industrial&Engineering Chemistry,2018,100(62):352-361.
[2]Ahlqvist M,Bo L,Hayes M A,et al.Early human in vivo pharmacokinetic predictions in drug discovery[J].Drug Metabolism&Pharmacokinetics,2018,33(1):S43.
[3]Rijal G,Li W.3D Scaolds in breast cancer research[J].Biomaterials,2016,37(81):135-156
[4]Hoarau-Véchot J,Rafii A,Touboul C,et al.Halfway between2DandAnimalModels:Are3DCultures theIdealTooltoStudyCancer-Microenvironment Interactions?[J].InternationalJournalofMolecular Sciences,2018,19(1):181.
[5]Lv D,Hu Z,Lu L,et al.Three-dimensional cell culture:A powerful tool in tumor research and drug discovery(Review)[J].OncologyLetters,2017,36(14):6999-7010.
[6]Meli L,Jordan E T,Clark D S,et al.Influence of a ThreeDimensional,Microarray Environment on Human Cell Culture in Drug Screening Systems[J].Biomaterials,2012,33(35):9087-9096.
[7]Florczyk S J,Simon M,Juba D,et al.A Bioinformatics 3D Cellular Morphotyping Strategy for Assessing Biomaterial Scaffold Niches[J].Acs Biomaterials Science&Engineering,2017,3(10):2302-2313.
[8]Zhang B,Li Y,Wang G,et al.Fabrication of agarose concave petridish for 3D-culture microarray method for spheroids formation of hepatic cells[J].Journal of Materials Science Materials in Medicine,2018,29(5):49.
[9]Soares C P,Midlej V,Benchimol M,et al.2D and 3Dorganized cardiac cells shows differences in cellular morphology,adhesion junctions, presence of myofibrils and protein expression[J].Plos One,2012,7(5):65.
[10]Li G N,Livi L L,Gourd C M,et al.Genomic and morphological changes of neuroblastoma cells in response to three-dimensional matrices[J].Tissue Engineering Part A,2007,13(5):1035-1047.
[11]Li S,Lao J,Chen BP,et al.Genomic analysis of smooth muscle cells in 3-dimensional collagen matrix[J].Faseb Journal Official Publication of the Federation of American Societies for Experimental Biology,2003,17(1):97.
[12]Peyton S R,Kim P D,Ghajar C M,et al.The Effects of Matrix Stiffness and RhoA on the Phenotypic Plasticity of Smooth Muscle Cells in a 3-D Biosynthetic Hydrogel System[J].Biomaterials,2008,29(17):2597.
[13]Wang B,Zhao Y,Lin H,et al.Phenotypical analysis of adult rat olfactory ensheathing cells on 3-D collagen scaffolds[J].Neuroscience Letters,2006,401(1–2):65-70.
[14]DebebBG,ZhangX,KrishnamurthyS,etal.Characterizing cancer cells with cancer stem celllike features in 293T human embryonic kidney cells[J].Molecular Cancer,9,2010,9(1):180.
[15]Juillerat-Jeanneret L,Bernasconi CC,Bricod C,et al.Heterogeneity of human glioblastoma:glutathioneS-transferase and methylguanine-methyltransferase.[J].Cancer Investigation,2008,26(6):597-609.
[16]ChingTe Kuo,ChiLing Chiang,Ruby YunJu Huang,etal.Configurable2Dand3Dspheroidtissue cultures on bioengineered surfaces with acquisition ofepithelial|[ndash]|mesenchymaltransition characteristics[J].Npg Asia Material,2012,50(4):27.
[17]G h o s hS,S p a g n o l iGC,M a r t i nI,e ta l.Three‐dimensionalcultureofmelanomacells profoundly affects gene expression profile:A high density oligonucleotide array study[J].Journal of Cellular Physiology,2005,204(2):522-531.
[18]Debnath J,Brugge J S.Modelling glandular epithelial cancers in three-dimensional cultures[J].Nature Reviews Cancer,2005,5(9):675-88.
[19]Boxberger H J,Meyer T F.A new method for the 3‐D in vitro growth of human RT112bladder carcinoma cells using the alginate culture technique[J].Biology of the Cell,1994,82(2-3):109-119.
[20]Lan S F,Safiejko-Mroczka B,Starly B.Long-term cultivation of HepG2 liver cells encapsulated in alginate hydrogels:a study of cell viability,morphology and drug metabolism[J].ToxicologyinVitro,2010,24(4):1314-1323.
[21]Labonia G J,Lockwood S Y,Heller A A,et al.Drug penetration and metabolism in 3-dimensional cell cultures treated in a 3D printed fluidic device:Assessment of irinotecan via MALDI imaging mass spectrometry[J].Proteomics,2016,16(11-12):1814-1821.
[22]He F L,Li D W,He J,et al.A novel layer-structured scaffold with large pore sizes suitable for 3D cell culture prepared by near-field electrospinning.[J].Materials Science&EngineeringCMaterialsforBiological Applications,2018,77(86):18.
[23]Choi Y J,Kim H,Kim J W,et al.Hepatic esterase activity is increased in hepatocyte-like cells derived from human embryonic stem cells using a 3D culture system[J].Biotechnology Letters,2018,40(2):1-9.
[24]Castillo G,Jiang X.Abstract 5447:Association of the hedgehog signal pathway to Gefitinib sensitivity in a 3D cancer cell lines screening[J].Cancer Research,2015,75(12):5852-5862.
[25]Shoemaker J T,Vukasinovic J.Abstract 4080:Cytochrome P450 enzyme activity is enhanced in hepatocytes grown using a perfused 3D cell culture drug screening system[J].Cancer Research,2017,77(13):4080.
[26]Abefukasawa N,Otsuka K,Aihara A,et al.Novel 3D Liquid Cell Culture Method for Anchorage-independent CellGrowth,CellImagingandAutomatedDrug Screening[J].Scientific Reports,2018,8(1):3627.
[27]Souza A G,Silva I,Camposfernandez E,et al.Comparative Assay of 2D and 3D Cell Culture Models:roliferation,Gene Expression and Anticancer Drug Response.[J].Current Pharmaceutical Design,2018,24(9):17-18.
[28]Han J,Oh S,Hoang HH,et al.Recapitulation of cancer stem cell niches in glioblastoma on 3D microfluidic cell culture devices under gravity-driven perfusion[J].Journal of Industrial&Engineering Chemistry,2018,100(62):352-361.
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