类器官研究进展及应用
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  • 英文篇名:Research progress in organoids and applications
  • 作者:董研博 ; 王健 ; 郑梦竹 ; 刘良发 ; 李山虎
  • 英文作者:DONG Yan-bo;WANG Jian;ZHENG Meng-zhu;LIU Liang-fa;LI Shan-hu;Department of Otolaryngology, Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University;Department of Cell Engineering, Institute of Biotechnology,Academy of Military Medical Sciences, Academy of Military Sciences;
  • 关键词:类器官 ; 三维培养 ; 干细胞 ; 药物筛选 ; 个体化治疗
  • 英文关键词:organoid;;three-dimensional culture;;stem cell;;drug screening;;personalized therapy
  • 中文刊名:YLBS
  • 英文刊名:Chinese Journal of Pharmacology and Toxicology
  • 机构:首都医科大学附属北京友谊医院耳鼻咽喉头颈外科;军事科学院军事医学研究院生物工程研究所细胞工程实验室;
  • 出版日期:2019-02-15
  • 出版单位:中国药理学与毒理学杂志
  • 年:2019
  • 期:v.33
  • 基金:国家自然科学基金(81672640);国家自然科学基金(81772750);; 国家科技重大专项(2018ZX09101001-003);; 首都医科大学附属北京友谊医院科研启动基金(yydszx2015-02)~~
  • 语种:中文;
  • 页:YLBS201902011
  • 页数:9
  • CN:02
  • ISSN:11-1155/R
  • 分类号:74-82
摘要
类器官是一种新型体外研究模型,由干细胞或肿瘤细胞在三维培养条件下自我组装而成。它能够高度模拟原位组织的生理结构和功能,经长期传代保持遗传信息的稳定,因此类器官在构建疾病模型、药物筛选及个体化医疗等方面具有广阔前景。目前,食道、胃、肠、肝、胰、前列腺和乳腺等结构的类器官和相应的肿瘤类器官均已面世,开拓了体外培养的新平台。本文将对类器官的类型及其在生物医学领域的应用做一综述。
        An organoid is a novel in vitro model, formed by self-organization of stem cells or tumor cells under three-dimension culture. It recapitulates many aspects of structural organization and functionality of its in vivo organ counterparts and maintains the stability of genetic materials under long-term culture, thus holding great promise for modeling disease, drug screening and personalized medicine.So far, normal and tumor organoids from structures such as esophagus, stomach, intestine, liver, pancreas and prostate and mammary gland have been established, providing a new culture platform in vitro. This article reviews the classification and biomedical applications of organoids.
引文
[1]Kamb A. What′s wrong with our cancer models?[J]. Nat Rev Drug Discov,2005,4(2):161-165.
    [2]Shanks N,Greek R,Greek J. Are animal models predictive for humans?[J/OL]. Philos Ethics Humanit Med,2009,4:2(2009-01-15). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2642860/
    [3]Lancaster MA,Knoblich JA. Organogenesis in a dish:modeling development and disease using organoid technologies[J/OL]. Science,2014,345(6194):1247125(2014-07-18). http://science.sciencemag.org/content/345/6194/1247125.long
    [4]Fatehullah A,Tan SH,Barker N. Organoids as an in vitro model of human development and disease[J]. Nat Cell Biol,2016,18(3):246-254.
    [5]Li ML,Aggeler J,Farson DA,Hatier C,Hassel J,Bissell MJ. Influence of a reconstituted basement membrane and its components on casein gene expression and secretion in mouse mammary epithelial cells[J]. Proc Natl Acad Sci USA,1987,84(1):136-140.
    [6]Pellegrini G,Traverso CE,Franzi AT,Zingirian M,Cancedda R,De Luca M. Long-term restoration of damaged corneal surfaces with autologous cultivated corneal epithelium[J]. Lancet, 1997, 349(9057):990-993.
    [7]Sato T,Vries RG,Snippert HJ,van de Wetering M,Barker N,Stange DE,et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche[J]. Nature,2009,459(7244):262-265.
    [8]Barker N, van Es JH, Kuipers J, Kujala P,van den Born M,Cozijnsen M,et al. Identification of stem cells in small intestine and colon by marker gene Lgr5[J]. Nature,2007,449(7165):1003-1007.
    [9]Sato T,Stange DE,Ferrante M,Vries RG,Van Es JH,Van den Brink S,et al. Long-term expansion of epithelial organoids from human colon,adenoma,adenocarcinoma,and Barrett′s epithelium[J]. Gastroenterology,2011,141(5):1762-1772.
    [10]Werner S,Vu HT,Rink JC. Self-organization in development, regeneration and organoids[J].Curr Opin Cell Biol,2017,44:102-109.
    [11]Clevers H,Loh KM,Nusse R. Stem cell signaling.An integral program for tissue renewal and regeneration:wnt signaling and stem cell control[J/OL].Science,2014,346(6205):1248012(2014-10-03).http://science.sciencemag.org/content/346/6205/1248012.long
    [12]Aihara E,Mahe MM,Schumacher MA,Matthis AL,Feng R,Ren W,et al. Characterization of stem/progenitor cell cycle using murine circumvallate papilla taste bud organoid[J/OL]. Sci Rep,2015,5:17185(2015-11-24). https://www. ncbi. nlm. nih.gov/pmc/articles/PMC4665766/
    [13]Barker N,Huch M,Kujala P,van de Wetering M,Snippert HJ,van Es JH,et al. Lgr5+ve stem cells drive self-renewal in the stomach and build longlived gastric units in vitro[J]. Cell Stem Cell,2010,6(1):25-36.
    [14]Stange DE,Koo BK,Huch M,Sibbel G,Basak O,Lyubimova A,et al. Differentiated Troy+chief cells act as reserve stem cells to generate all lineages of the stomach epithelium[J]. Cell,2013,155(2):357-368.
    [15]Sato T,Clevers H. Growing self-organizing miniguts from a single intestinal stem cell:mechanism and applications[J]. Science,2013,340(6137):1190-1194.
    [16]Huch M,Dorrell C,Boj SF,van Es JH,Li VS,van de Wetering M,et al. In vitro expansion of single Lgr5+liver stem cells induced by Wnt-driven regeneration[J]. Nature,2013,494(7436):247-250.
    [17]Huch M,Bonfanti P,Boj SF,Sato T,Loomans CJ,van de Wetering M,et al. Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis[J]. EMBO J,2013,32(20):2708-2721.
    [18]Karthaus WR,Iaquinta PJ,Drost J,Gracanin A,van Boxtel R,Wongvipat J,et al. Identification of multipotent luminal progenitor cells in human prostate organoid cultures[J]. Cell,2014,159(1):163-175.
    [19]Hisha H, Tanaka T, Kanno S, Tokuyama Y,Komai Y,Ohe S,et al. Establishment of a novel lingual organoid culture system:generation of organoids having mature keratinized epithelium from adult epithelial stem cells[J/OL]. Sci Rep,2013,3:3224(2013-11-15). https://www. ncbi. nlm. nih.gov/pmc/articles/PMC3828633/
    [20]Nanduri LS,Baanstra M,Faber H,Rocchi C,Zwart E,de Haan G,et al. Purification and ex vivo expansion of fully functional salivary gland stem cells[J]. Stem Cell Reports,2014,3(6):957-964.
    [21]Thomson JA1, Itskovitz-Eldor J, Shapiro SS,Waknitz MA,Swiergiel JJ,Marshall VS,et al.Embryonic stem cell lines derived from human blastocysts[J]. Science,1998,282(5391):1145-1147.
    [22]Blau HM,Chiu CP,Webster C. Cytoplasmic activation of human nuclear genes in stable heterocaryons[J]. Cell,1983,32(4):1171-1180.
    [23]Chung YG,Eum JH,Lee JE,Shim SH,Sepilian V,Hong SW,et al. Human somatic cell nuclear transfer using adult cells[J]. Cell Stem Cell,2014,14(6):777-780.
    [24]Takahashi K,Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors[J]. Cell,2006,126(4):663-676.
    [25]Noguchi TK,Ninomiya N,Sekine M,Komazaki S,Wang PC,Asashima M,et al. Generation of stomach tissue from mouse embryonic stem cells[J]. Nat Cell Biol,2015,17(8):984-993.
    [26]Antonica F,Kasprzyk DF,Opitz R,Iacovino M,Liao XH,Dumitrescu AM,et al. Generation of functional thyroid from embryonic stem cells[J].Nature,2012,491(7422):66-71.
    [27]Takebe T,Sekine K,Enomura M,Koike H,Kimura M,Ogaeri T,et al. Vascularized and functional human liver from an iPSC-derived organ bud transplant[J]. Nature,2013,499(7459):481-484.
    [28]Spence JR,Mayhew CN,Rankin SA,Kuhar MF,Vallance JE,Tolle K,et al. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro[J]. Nature,2011,470(7332):105-109.
    [29]Dye BR,Hil DR,Ferguson MA,Tsai YH,Nagy MS,Dyal R. et al. In vitro generation of human pluripotent stem cell derived lung organoids[J/OL]. Elife,2015, 4:e05098(2015-03-04). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370217/
    [30]Lancaster MA,Renner M,Martin CA,Wenzel D,Bicknell LS,Hurles ME,et al. Cerebral organoids model human brain development and microcephaly[J]. Nature,2013,501(7467):373-379.
    [31]Suga H,Kadoshima T,Minaguchi M,Ohgushi M,Soen M,Nakano T,et al. Self-formation of functional adenohypophysis in three-dimensional culture[J]. Nature,2011,480(7375):57-62.
    [32]Koehler KR,Mikosz AM,Molosh AI,Patel D,Hashino E. Generation of inner ear sensory epithelia from pluripotent stem cel s in 3D culture[J]. Nature,2013,500(7461):217-221.
    [33]Eiraku M,Takata N,Ishibashi H,Kawada M,Sakakura E,Okuda S,et al. Self-organizing optic-cup morphogenesis in three-dimensional culture[J].Nature,2011,472(7341):51-56.
    [34]Kirwan P,Turner-Bridger B,Peter M,Momoh A,Arambepola D,Robinson HP,et al. Development and function of human cerebral cortex neural networks from pluripotent stem cells in vitro[J]. Development,2015,142(18):3178-3187.
    [35]Takasato M,Er PX,Chiu HS,Maier B,Baillie GJ,Ferguson C,et al. Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis[J]. Nature,2015,526(7574):564-568.
    [36]Gao D,Vela I,Sboner A,Iaquinta PJ,Karthaus WR,Gopalan A,et al. Organoid cultures derived from patients with advanced prostate cancer[J]. Cell,2014,159(1):176-187.
    [37]Fujii M,Shimokawa M,Date S,Takano A,Matano M,Nanki K,et al. A Colorectal tumor organoid library demonstrates progressive loss of niche factor requirements during tumorigenesis[J]. Cell Stem Cell,2016,18(6):827-838.
    [38]Li X,Francies HE,Secrier M,Perner J,Miremadi A,Galeano-Dalmau N,et al. Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics[J/OL]. Nat Commun,2018,9(1):2983(2018-07-30). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065407/
    [39]Bartfeld S,Bayram T,van de Wetering M,Huch M,Begthel H,Kujala P,et al. In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection[J]. Gastroenterology, 2015,148(1):126-136,e6.
    [40]Broutier L, Mastrogiovanni G, Verstegen MM,Francies HE,GavarróLM,Bradshaw CR1,et al.Human primary liver cancer-derived organoid cultures for disease modeling and drug screening[J]. Nat Med,2017,23(12):1424-1435.
    [41]Huang L, Holtzinger A, Jagan I, BeGora M,Lohse I,Ngai N,et al. Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell-and patient-derived tumor organoids[J].Nat Med,2015,21(11):1364-1371.
    [42]Sachs N,de Ligt J,Kopper O,Gogola E,Bounova G,Weeber F,et al. A living biobank of breast cancer organoids captures disease heterogeneity[J]. Cel,2018,172(1-2):373-386,e10.
    [43]Turco MY,Gardner L,Hughes J,Cindrova-Davies T,Gomez MJ,Farrell L,et al. Long-term,hormoneresponsive organoid cultures of human endometrium in a chemically defined medium[J]. Nat Cell Biol,2017,19(5):568-577.
    [44]Mondrinos MJ, Jones PL, Finck CM, Lelkes PI.Engineering de novo assembly of fetal pulmonary organoids[J]. Tissue Eng Part A,2014,20(21-22):2892-2907.
    [45]Grün D,Lyubimova A,Kester L,Wiebrands K,Basak O,Sasaki N,et al. Single-cell messenger RNA sequencing reveals rare intestinal cell types[J]. Nature,2015,525(7568):251-255.
    [46]Nadauld LD, Garcia S, Natsoulis G, Bell JM,Miotke L,Hopmans ES,et al. Metastatic tumor evolution and organoid modeling implicate TGFBR2 as a cancer driver in diffuse gastric cancer[J/OL].Genome Biol,2014,15(8):428(2014-08-27).https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145231/
    [47]Li X,Nadauld L,Ootani A,Corney DC,Pai RK,Gevaert O,et al. Oncogenic transformation of diverse gastrointestinal tissues in primary organoid culture[J]. Nat Med,2014,20(7):769-777.
    [48]Barretina J,Caponigro G,Stransky N,Venkatesan K,Margolin AA,Kim S,et al. The cancer cel line encyclopedia enables predictive modelling of anticancer drug sensitivity[J]. Nature,2012,483(7391):603-607.
    [49]Vlachogiannis G,Hedayat S,Vatsiou A,Jamin Y,Fernández-Mateos J,Khan K,et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers[J]. Science,2018,359(6378):920-926.
    [50]Verissimo CS,Overmeer RM,Ponsioen B,Drost J,Mertens S,Verlaan-Klink I,et al. Targeting mutant RAS in patient-derived colorectal cancer organoids by combinatorial drug screening[J/OL]. Elife,2016,5:e18489(2016-11-15). https://www. ncbi.nlm.nih.gov/pmc/articles/PMC5127645/
    [51]Shenoy TR,Boysen G,Wang MY,Xu QZ,Guo W,Koh FM,et al. CHD1 loss sensitizes prostate cancer to DNA damaging therapy by promoting error-prone double-strand break repair[J]. Ann Oncol,2017,28(7):1495-1507.
    [52]Ballet F. Hepatotoxicity in drug development:detection, significance and solutions[J]. J Hepatol,1997,26(Suppl 2):26-36.
    [53]Huch M,Gehart H,van Boxtel R,Hamer K,Blokzijl F,Verstegen MM,et al. Long-term culture of genome-stable bipotent stem cells from adult human liver[J]. Cell,2015,160(1-2):299-312.
    [54]Eder A,Vollert I,Hansen A,Eschenhagen T.Human engineered heart tissue as a model system for drug testing[J]. Adv Drug Deliv Rev,2016,96:214-224.
    [55]Yui S,Nakamura T,Sato T,Nemoto Y,Mizutani T,Zheng X,et al. Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5+stem cel[J]. Nat Med,2012,18(4):618-623.
    [56]Sugimoto S,Ohta Y,Fujii M,Matano M,Shimokawa M,Nanki K,et al. Reconstruction of the human colon epithelium in vivo[J]. Cell Stem Cell,2018,22(2):171-176,e5.
    [57]Nakamura T,Sato T. Advancing intestinal organoid technology toward regenerative medicine[J]. Cell Mol Gastroenterol Hepatol,2017,5(1):51-60.
    [58]Nantasanti S,Spee B,Kruitwagen HS,Chen C,Geijsen N,Oosterhoff LA,et al. Disease modeling and gene therapy of copper storage disease in canine hepatic organoids[J]. Stem Cell Reports,2015,5(5):895-907.
    [59]Wang YI,Abaci HE,Shuler ML. Microfluidic bloodbrain barrier model provides in vivo-like barrier properties for drug permeability screening[J].Biotechnol Bioeng,2017,114(1):184-194.
    [60]Skardal A,Murphy SV,Devarasetty M,Mead I,Kang HW,Seol YJ,et al. Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform[J/OL]. Sci Rep,2017,7(1):8837(2017-08-18).https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562747/
    [61]Workman MJ,Mahe MM,Trisno S,Poling HM,Watson CL,Sundaram N,et al. Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system[J]. Nat Med,2017,23(1):49-59.
    [62]Dijkstra KK,Cattaneo CM,Weeber F,Chalabi M,van de Haar J,Fanchi LF,et al. Generation of tumorreactive T cells by co-culture of peripheral blood lymphocytes and tumor organoids[J]. Cell,2018,174(6):1586-1598,e12.
    [63]Seino T,Kawasaki S,Shimokawa M,Tamagawa H,Toshimitsu K,Fuji M,et al. Human pancreatic tumor organoids reveal loss of stem cell niche factor dependence during disease progression[J]. Cell Stem Cell,2018,22(3):454-467,e6.
    [64]Gjorevski N, Sachs N, Manfrin A, Giger S,Bragina ME,Ordó?ez-Morán P,et al. Designer matrices for intestinal stem cel and organoid culture[J]. Nature,2016,539(7630):560-564.
    [65]Janda CY,Dang LT,You C,Chang J,de Lau W,Zhong ZA,et al. Surrogate Wnt agonists that phenocopy canonical wnt andβ-catenin signaling[J]. Nature,2017,545(7653):234-237.
    [66]Hubert CG, Rivera M, Spangler LC, Wu Q,Mack SC,Prager BC,et al. A three-dimensional organoid culture system derived from human glioblastomas recapitulates the hypoxic gradients and cancer stem cell heterogeneity of tumors found in vivo[J].Cancer Res,2016,76(8):2465-2477.

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