任悦3,
沈素3,
殷诺雅1,2,
Francesco Faiola1,2,
张杨3
1. 中国科学院生态环境研究中心, 环境化学与生态毒理学国家重点实验室, 北京 100085;
2. 中国科学院大学资源与环境学院, 北京 100049;
3. 首都医科大学附属北京友谊医院药学部, 北京 100050
作者简介: 杨仁君(1990-),男,博士,研究方向为干细胞毒理学,E-mail:313659164@qq.com.
基金项目: 国家自然科学基金面上项目(21577166,21876197);国家自然科学基金青年科学基金资助项目(21707160)中图分类号: X171.5
Application and Prospect of Human Pluripotent Stem Cells in Risk Assessment of Environmental Pollutants
Yang Renjun1,2,Ren Yue3,
Shen Su3,
Yin Nuoya1,2,
Francesco Faiola1,2,
Zhang Yang3
1. State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China;
2. College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China;
3. Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
CLC number: X171.5
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摘要:在环境污染问题日益严峻的今天,人们亟需一套高效的毒理学评价体系来全面评估各类环境污染物的毒性效应和致毒机制,并阐明化合物结构与毒性效应之间的关系,进而指导安全化合物的合成。人多能干细胞(hPSCs)具有近乎无限的增殖能力和分化成所有成体细胞的潜能,近年来在毒理学的应用中崭露头角,显现出极大的应用潜力。由hPSCs分化而来的细胞可以代替原代细胞进行高通量的毒理学研究;hPSCs分化模型便于在体外研究环境污染物暴露对人体胚胎发育过程的毒性;基于hPSCs构建的类器官技术也使环境污染物的器官毒性研究成为可能。hPSCs在环境污染物风险评估中有很高的应用价值。
关键词: 环境污染物/
人多能干细胞/
发育毒性/
器官毒性
Abstract:With environmental issues being increasingly serious, an efficient toxicology evaluation system is urgently needed to comprehensively evaluate the toxic effects of various environmental pollutants, reveal the toxic mechanism, discern the relationship between the structure and toxic effects of chemicals, and thus guide the synthesis of safe compounds. In recent years, the application of human pluripotent stem cells (hPSCs) in toxicity research has emerged showing great potential. hPSCs possess almost unlimited proliferation ability and the potential to differentiate into all the cell types of the adult. Cells differentiated from hPSCs can replace primary cells for toxicity research and the experiments can be carried out in a high-throughput manner. The differentiation model of hPSCs can be used to study the developmental toxicity of environmental pollutants to human embryos in vitro. In addition, technology breakthroughs of iPSC-based organoid construction make it possible to study the organ toxicity of environmental pollutants. Therefore, hPSCs possess great practical value in risk assessment of environmental pollutants.
Key words:environmental pollutants/
human pluripotent stem cells/
developmental toxicity/
organ toxicity.
Zhao X Y, Li W, Lv Z, et al. iPS cells produce viable mice through tetraploid complementation[J]. Nature, 2009, 461(7260):86-90 |
Evans M J, Kaufman M H. Establishment in culture of pluripotential cells from mouse embryos[J]. Nature, 1981, 292(5819):154-156 |
Laschinski G, Vogel R, Spielmann H. Cytotoxicity test using blastocyst-derived euploid embryonal stem cells:A new approach to in vitro teratogenesis screening[J]. Reproductive Toxicology, 1991, 5(1):57-64 |
Spielmann H, Pohl I, Doring B, et al. The embryonic stem cell test (EST), an in vitro embryotoxicity test using two permanent mouse cell lines:3T3 fibroblasts and embryonic stem cells[J]. Toxicology in Vitro, 1997, 10:119-127 |
Thomson J A, Itskovitz-Eldor J, Shapiro S S, et al. Embryonic stem cell lines derived from human blastocysts[J]. Science, 1998, 282(5391):1145-1147 |
Scholz G, Pohl I, Genschow E, et al. Embryotoxicity screening using embryonic stem cells in vitro:Correlation to in vivo teratogenicity[J]. Cells Tissues Organs, 1999, 165(3-4):203-211 |
Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors[J]. Cell, 2007, 131(5):861-872 |
Park I H, Arora N, Huo H, et al. Disease-specific induced pluripotent stem cells[J]. Cell, 2008, 134(5):877-886 |
Adler S, Pellizzer C, Hareng L, et al. First steps in establishing a developmental toxicity test method based on human embryonic stem cells[J]. Toxicology in Vitro, 2008, 22(1):200-211 |
Guo L, Abrams R M, Babiarz J E, et al. Estimating the risk of drug-induced proarrhythmia using human induced pluripotent stem cell-derived cardiomyocytes[J]. Toxicological Sciences, 2011, 123(1):281-289 |
Rowe R G, Daley G Q. Induced pluripotent stem cells in disease modelling and drug discovery[J]. Nature Reviews Genetics, 2019, 20(7):377-388 |
Pei Y, Peng J, Behl M, et al. Comparative neurotoxicity screening in human iPSC-derived neural stem cells, neurons and astrocytes[J]. Brain Research, 2016, 1638(Pt A):57-73 |
Rice D, Barone S Jr. Critical periods of vulnerability for the developing nervous system:Evidence from humans and animal models[J]. Environmental Health Perspectives, 2000, 108(Suppl 3):511-533 |
Kadereit S, Zimmer B, van Thriel C, et al. Compound selection for in vitro modeling of developmental neurotoxicity[J]. Frontiers in Bioscience (Landmark Ed.), 2012, 17:2442-2460 |
Colleoni S, Galli C, Gaspar J A, et al. Development of a neural teratogenicity test based on human embryonic stem cells:Response to retinoic acid exposure[J]. Toxicological Sciences, 2011, 124(2):370-377 |
Hoelting L, Scheinhardt B, Bondarenko O, et al. A 3-dimensional human embryonic stem cell (hESC)-derived model to detect developmental neurotoxicity of nanoparticles[J]. Archive of Toxicology, 2013, 87(4):721-733 |
Huang B, Ning S, Zhang Q, et al. Bisphenol A represses dopaminergic neuron differentiation from human embryonic stem cells through downregulating the expression of insulin-like growth factor 1[J]. Molecular Neurobiology, 2017, 54(5):3798-3812 |
Krug A K, Kolde R, Gaspar J A, et al. Human embryonic stem cell-derived test systems for developmental neurotoxicity:A transcriptomics approach[J]. Archive of Toxicology, 2013, 87(1):123-143 |
Chen H, Seifikar H, Larocque N, et al. Using a multi-stage hESC model to characterize BDE-47 toxicity during neurogenesis[J]. Toxicological Sciences, 2019, 171(1):221-234 |
Trevino L S, Katz T A. Endocrine disruptors and developmental origins of nonalcoholic fatty liver disease[J]. Endocrinology, 2018, 159(1):20-31 |
Liang S, Liang S, Yin N, et al. Establishment of a human embryonic stem cell-based liver differentiation model for hepatotoxicity evaluations[J]. Ecotoxicology and Environmental Safety, 2019, 174:353-362 |
van der Linde D, Konings E E, Slager M A, et al. Birth prevalence of congenital heart disease worldwide:A systematic review and meta-analysis[J]. Journal of the American College of Cardiology 2011, 58(21):2241-2247 |
Hoffman J I E, Kaplan S. The incidence of congenital heart disease[J]. Journal of the American College of Cardiology, 2002, 39(12):1890-1900 |
Fu H, Wang L, Wang J, et al. Dioxin and AHR impairs mesoderm gene expression and cardiac differentiation in human embryonic stem cells[J]. Science of the Total Environment, 2019, 651(Pt 1):1038-1046 |
Sant K E, Jacobs H M, Borofski K A, et al. Embryonic exposures to perfluorooctanesulfonic acid (PFOS) disrupt pancreatic organogenesis in the zebrafish, Danio rerio[J]. Environmental Pollution, 2017, 220(Pt B):807-817 |
Liu S, Yin N, Faiola F. PFOA and PFOS disrupt the generation of human pancreatic progenitor cells[J]. Environmental Science & Technology Letters, 2018, 5(5):237-242 |
Lind L, Zethelius B, Salihovic S, et al. Circulating levels of perfluoroalkyl substances and prevalent diabetes in the elderly[J]. Diabetologia, 2014, 57(3):473-479 |
Karnes C, Winquist A, Steenland K. Incidence of typeⅡ diabetes in a cohort with substantial exposure to perfluorooctanoic acid[J]. Environmental Research, 2014, 128:78-83 |
Domazet S L, Grontved A, Timmermann A G, et al. Longitudinal associations of exposure to perfluoroalkylated substances in childhood and adolescence and indicators of adiposity and glucose metabolism 6 and 12 years later:The European Youth Heart Study[J]. Diabetes Care, 2016, 39(10):1745-1751 |
Conway B, Innes K E, Long D. Perfluoroalkyl substances and beta cell deficient diabetes[J]. Journal of Diabetes and Its Complications, 2016, 30(6):993-998 |
Cardenas A, Gold D R, Hauser R, et al. Plasma concentrations of per- and polyfluoroalkyl substances at baseline and associations with glycemic indicators and diabetes incidence among high-risk adults in the diabetes prevention program trial[J]. Environmental Health Perspectives, 2017, 125(10):107001 |
Gurtner G C, Werner S, Barrandon Y, et al. Wound repair and regeneration[J]. Nature, 2008, 453(7193):314-321 |
Culton D A, Qian Y, Li N, et al. Advances in pemphigus and its endemic pemphigus foliaceus (Fogo Selvagem) phenotype:A paradigm of human autoimmunity[J]. Journal of Autoimmunity, 2008, 31(4):311-324 |
Cheng Z, Liang X, Liang S, et al. A human embryonic stem cell-based in vitro model revealed that ultrafine carbon particles may cause skin inflammation and psoriasis[J]. Journal of Environmental Sciences, 2020, 87:194-204 |
Haycock J W. 3D cell culture:A review of current approaches and techniques[J]. Methods in Molecular Biology, 2011, 695:1-15 |
Lancaster M A, Knoblich J A. Organogenesis in a dish:Modeling development and disease using organoid technologies[J]. Science, 2014, 345(6194):1247125 |
Takebe T, Sekine K, Enomura M, et al. Vascularized and functional human liver from an iPSC-derived organ bud transplant[J]. Nature, 2013, 499(7459):481-484 |
Pasca S P. The rise of three-dimensional human brain cultures[J]. Nature, 2018, 553(7689):437-445 |
Richards D J, Coyle R C, Tan Y, et al. Inspiration from heart development:Biomimetic development of functional human cardiac organoids[J]. Biomaterials, 2017, 142:112-123 |
Huch M, Gehart H, van Boxtel R, et al. Long-term culture of genome-stable bipotent stem cells from adult human liver[J]. Cell, 2015, 160(1-2):299-312 |
Leite S B, Roosens T, El Taghdouini A, et al. Novel human hepatic organoid model enables testing of drug-induced liver fibrosis in vitro[J]. Biomaterials, 2016, 78:1-10 |
Boj S F, Hwang C I, Baker L A, et al. Organoid models of human and mouse ductal pancreatic cancer[J]. Cell, 2015, 160(1-2):324-338 |
Barkauskas C E, Chung M I, Fioret B, et al. Lung organoids:Current uses and future promise[J]. Development, 2017, 144(6):986-997 |
Taguchi A, Nishinakamura R. Higher-order kidney organogenesis from pluripotent stem cells[J]. Cell Stem Cell, 2017, 21(6):730-746.e6 |
Kessler M, Hoffmann K, Brinkmann V, et al. The Notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids[J]. Nature Communication, 2015, 6:8989 |
Zhong X, Gutierrez C, Xue T, et al. Generation of three-dimensional retinal tissue with functional photoreceptors from human iPSCs[J]. Nature Communications, 2014, 5:4047 |
Foster J W, Wahlin K, Adams S M, et al. Cornea organoids from human induced pluripotent stem cells[J]. Scientific Reports, 2017, 7:41286 |
Maimets M, Rocchi C, Bron R, et al. Long-term in vitro expansion of salivary gland stem cells driven by Wnt signals[J]. Stem Cell Reports, 2016, 6(1):150-162 |
Turco M Y, Gardner L, Hughes J, et al. Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium[J].Nature Cell Biology, 2017, 19(5):568-577 |
Titmarsh D M, Nurcombe V, Cheung C, et al. Vascular cells and tissue constructs derived from human pluripotent stem cells for toxicological screening[J]. Stem Cells and Development, 2019, 28(20):1347-1364 |
Schwartz M P, Hou Z, Propson N E, et al. Human pluripotent stem cell-derived neural constructs for predicting neural toxicity[J].Proceedings of the National Academy of Sciences of the United States of America, 2015, 112(40):12516-12521 |
Mills R J, Parker B L, Quaife-Ryan G A, et al. Drugscreening in human PSC-cardiac organoids identifies pro-proliferative compounds acting via the mevalonate pathway[J]. Cell Stem Cell, 2019, 24(6):895-907.e6 |
李朋彦, 李春雨, 陆小华, 等. 基于类器官3D培养和高内涵成像的药物肝毒性评价模型研究[J]. 药学学报, 2017, 52(7):1055-1062Li P Y, Li C Y, Lu X H, et al. The three dimensional organoids-based high content imaging model for hepatotoxicity assessment[J]. Acta Pharmaceutica Sinica, 2017, 52(7):1055-1062(in Chinese) |
Czerniecki S M, Cruz N M, Harder J L, et al. High-throughput screening enhances kidney organoid differentiation from human pluripotent stem cells and enables automated multidimensional phenotyping[J]. Cell Stem Cell, 2018, 22(6):929-940.e4 |
Li X J, Valadez A V, Zuo P, et al. Microfluidic 3D cell culture:Potential application for tissue-based bioassays[J]. Bioanalysis, 2012, 4(12):1509-1525 |
van Duinen V, Trietsch S J, Joore J, et al. Microfluidic 3D cell culture:From tools to tissue models[J]. Current Opinion in Biotechnology, 2015, 35:118-126 |
Huh D, Matthews B D, Mammoto A, et al. Reconstituting organ-level lung functions on a chip[J]. Science, 2010, 328(5986):1662-1668 |
Park S E, Georgescu A, Huh D. Organoids-on-a-chip[J]. Science, 2019, 364(6444):960-965 |