[논문]Current Challenges Associated with the Use of Human Induced Pluripotent Stem Cell-Derived Organoids in Regenerative Medicine

Lee, Hana; Son, Mi-Young

doi:10.15283/ijsc20140

[국내논문] Current Challenges Associated with the Use of Human Induced Pluripotent Stem Cell-Derived Organoids in Regenerative Medicine 원문보기

International journal of stem cells, v.14 no.1, 2021년, pp.9 - 20

Lee, Hana (Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea) , Son, Mi-Young (Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea)

Abstract ▼ AI-Helper

Innovative advances in stem cell research have resulted in the development of organoids, which are widely used as in vitro models of human organ development and for disease. The long-term goals of scientists include the generation of high-quality organoids with properties like those of native organs, and to expand their use to a variety of applications such as drug discovery and organoid-based cell therapy. In particular, the combination of human induced pluripotent stem cell (iPSC)-derived organoids with the recently developed genome engineering, biotechnology serve as an attractive platform in precision medicine. This review briefly summarizes the generation of organoids derived mostly from iPSCs without ethical issues, and describes the applications and technological advances of organoids under their differentiation and culture conditions. We also discuss the approaches to improve the organoid models, and how organoids can recapitulate mature organ systems of the human body for regenerative medicine. Finally, the future perspectives and remaining challenges in the field have been discussed to provide a better understanding of the potential applications of organoids.

Keyword

참고문헌 (90)

1 Clevers H 2016 Modeling development and disease with organoids Cell 165 1586 1597 10.1016/j.cell.2016.05.082 27315476

상세보기
2 Lancaster MA Knoblich JA 2014 Organogenesis in a dish: modeling development and disease using organoid technologies Science 345 1247125 10.1126/science.1247125 25035496

상세보기
3 Sasai Y 2013 Cytosystems dynamics in self-organization of tissue architecture Nature 493 318 326 10.1038/nature11859 23325214

상세보기
4 Yu J Vodyanik MA Smuga-Otto K Antosiewicz-Bourget J Frane JL Tian S Nie J Jonsdottir GA Ruotti V Stewart R Slukvin II Thomson JA 2007 Induced pluripotent stem cell lines derived from human somatic cells Science 318 1917 1920 10.1126/science.1151526 18029452

상세보기
5 Orkin RW Gehron P McGoodwin EB Martin GR Valentine T Swarm R 1977 A murine tumor producing a matrix of basement membrane J Exp Med 145 204 220 10.1084/jem.145.1.204 830788

상세보기
6 Ehrmann RL Gey GO 1956 The growth of cells on a transparent gel of reconstituted rat-tail collagen J Natl Cancer Inst 16 1375 1403 13320119
7 Hughes CS Postovit LM Lajoie GA 2010 Matrigel: a complex protein mixture required for optimal growth of cell culture Proteomics 10 1886 1890 10.1002/pmic.200900758 20162561

상세보기
8 Freytes DO Martin J Velankar SS Lee AS Badylak SF 2008 Preparation and rheological characterization of a gel form of the porcine urinary bladder matrix Biomaterials 29 1630 1637 10.1016/j.biomaterials.2007.12.014 18201760

상세보기
9 Spence JR Mayhew CN Rankin SA Kuhar MF Vallance JE Tolle K Hoskins EE Kalinichenko VV Wells SI Zorn AM Shroyer NF Wells JM 2011 Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro Nature 470 105 109 10.1038/nature09691 21151107

상세보기
10 Zhong X Gutierrez C Xue T Hampton C Vergara MN Cao LH Peters A Park TS Zambidis ET Meyer JS Gamm DM Yau KW Canto-Soler MV 2014 Generation of three-dimensional retinal tissue with functional photoreceptors from human iPSCs Nat Commun 5 4047 10.1038/ncomms5047 24915161

상세보기
11 Takebe T Sekine K Enomura M Koike H Kimura M Ogaeri T Zhang RR Ueno Y Zheng YW Koike N Aoyama S Adachi Y Taniguchi H 2013 Vascularized and functional human liver from an iPSC-derived organ bud transplant Nature 499 481 484 10.1038/nature12271 23823721

상세보기
12 Lancaster MA Renner M Martin CA Wenzel D Bicknell LS Hurles ME Homfray T Penninger JM Jackson AP Knoblich JA 2013 Cerebral organoids model human brain development and microcephaly Nature 501 373 379 10.1038/nature12517 23995685

상세보기
13 McCracken KW Catá EM Crawford CM Sinagoga KL Schumacher M Rockich BE Tsai YH Mayhew CN Spence JR Zavros Y Wells JM 2014 Modelling human development and disease in pluripotent stem-cell-derived gastric organoids Nature 516 400 404 10.1038/nature13863 25363776

상세보기
14 Miller AJ Hill DR Nagy MS Aoki Y Dye BR Chin AM Huang S Zhu F White ES Lama V Spence JR 2018 In vitro induction and in vivo engraftment of lung bud tip progenitor cells derived from human pluripotent stem cells Stem Cell Reports 10 101 119 10.1016/j.stemcr.2017.11.012 29249664

상세보기
15 Morizane R Lam AQ Freedman BS Kishi S Valerius MT Bonventre JV 2015 Nephron organoids derived from human pluripotent stem cells model kidney development and injury Nat Biotechnol 33 1193 1200 10.1038/nbt.3392 26458176

상세보기
16 Hohwieler M Illing A Hermann PC Mayer T Stockmann M Perkhofer L Eiseler T Antony JS Müller M Renz S Kuo CC Lin Q Sendler M Breunig M Kleiderman SM Lechel A Zenker M Leichsenring M Rosendahl J Zenke M Sainz B Jr Mayerle J Costa IG Seufferlein T Kormann M Wagner M Liebau S Kleger A 2017 Human pluripotent stem cell-derived acinar/ductal organoids generate human pancreas upon orthotopic transplantation and allow disease modelling Gut 66 473 486 10.1136/gutjnl-2016-312423 27633923

상세보기
17 Koehler KR Nie J Longworth-Mills E Liu XP Lee J Holt JR Hashino E 2017 Generation of inner ear organoids containing functional hair cells from human pluripotent stem cells Nat Biotechnol 35 583 589 10.1038/nbt.3840 28459451

상세보기
18 Mills RJ Titmarsh DM Koenig X Parker BL Ryall JG Quaife-Ryan GA Voges HK Hodson MP Ferguson C Drowley L Plowright AT Needham EJ Wang QD Gregorevic P Xin M Thomas WG Parton RG Nielsen LK Launikonis BS James DE Elliott DA Porrello ER Hudson JE 2017 Functional screening in human cardiac organoids reveals a metabolic mechanism for cardiomyocyte cell cycle arrest Proc Natl Acad Sci U S A 114 E8372 E8381 10.1073/pnas.1707316114 28916735

상세보기
19 Kim Y Park N Rim YA Nam Y Jung H Lee K Ju JH 2018 Establishment of a complex skin structure via layered co-culture of keratinocytes and fibroblasts derived from induced pluripotent stem cells Stem Cell Res Ther 9 217 10.1186/s13287-018-0958-2 30103800

상세보기
20 Wimmer RA Leopoldi A Aichinger M Wick N Hantusch B Novatchkova M Taubenschmid J Hämmerle M Esk C Bagley JA Lindenhofer D Chen G Boehm M Agu CA Yang F Fu B Zuber J Knoblich JA Kerjaschki D Penninger JM 2019 Human blood vessel organoids as a model of diabetic vasculopathy Nature 565 505 510 10.1038/s41586-018-0858-8 30651639

상세보기
21 Dekkers JF Wiegerinck CL de Jonge HR Bronsveld I Janssens HM de Winter-de Groot KM Brandsma AM de Jong NW Bijvelds MJ Scholte BJ Nieuwenhuis EE van den Brink S Clevers H van der Ent CK Middendorp S Beekman JM 2013 A functional CFTR assay using primary cystic fibrosis intestinal organoids Nat Med 19 939 945 10.1038/nm.3201 23727931

상세보기
22 Yui S Nakamura T Sato T Nemoto Y Mizutani T Zheng X Ichinose S Nagaishi T Okamoto R Tsuchiya K Clevers H Watanabe M 2012 Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5 ＋ stem cell Nat Med 18 618 623 10.1038/nm.2695 22406745

상세보기
23 Freedman BS Brooks CR Lam AQ Fu H Morizane R Agrawal V Saad AF Li MK Hughes MR Werff RV Peters DT Lu J Baccei A Siedlecki AM Valerius MT Musunuru K McNagny KM Steinman TI Zhou J Lerou PH Bonventre JV 2015 Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids Nat Commun 6 8715 10.1038/ncomms9715 26493500

상세보기
24 Bartfeld S Bayram T van de Wetering M Huch M Begthel H Kujala P Vries R Peters PJ Clevers H 2015 In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection Gastroenterology 148 126 136.e6 10.1053/j.gastro.2014.09.042 25307862

상세보기
25 Drost J Karthaus WR Gao D Driehuis E Sawyers CL Chen Y Clevers H 2016 Organoid culture systems for prostate epithelial and cancer tissue Nat Protoc 11 347 358 10.1038/nprot.2016.006 26797458

상세보기
26 Boj SF Hwang CI Baker LA Chio II Engle DD Corbo V Jager M Ponz-Sarvise M Tiriac H Spector MS Gracanin A Oni T Yu KH van Boxtel R Huch M Rivera KD Wilson JP Feigin ME Öhlund D Handly-Santana A Ardito-Abraham CM Ludwig M Elyada E Alagesan B Biffi G Yordanov GN Delcuze B Creighton B Wright K Park Y Morsink FH Molenaar IQ Borel Rinkes IH Cuppen E Hao Y Jin Y Nijman IJ Iacobuzio-Donahue C Leach SD Pappin DJ Hammell M Klimstra DS Basturk O Hruban RH Offerhaus GJ Vries RG Clevers H Tuveson DA 2015 Organoid models of human and mouse ductal pancreatic cancer Cell 160 324 338 10.1016/j.cell.2014.12.021 25557080

상세보기
27 Chinta MS desJardins-Park HE Wan DC Longaker MT 2020 "Tissues in a dish": a review of organoids in plastic surgery Plast Reconstr Surg Glob Open 8 e2787 10.1097/GOX.0000000000002787 32440447

상세보기
28 Sugimoto S Ohta Y Fujii M Matano M Shimokawa M Nanki K Date S Nishikori S Nakazato Y Nakamura T Kanai T Sato T 2018 Reconstruction of the human colon epithelium in vivo Cell Stem Cell 22 171 176.e5 10.1016/j.stem.2017.11.012 29290616

상세보기
29 Sato T Vries RG Snippert HJ van de Wetering M Barker N Stange DE van Es JH Abo A Kujala P Peters PJ Clevers H 2009 Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche Nature 459 262 265 10.1038/nature07935 19329995

상세보기
30 Harrison SE Sozen B Christodoulou N Kyprianou C Zernicka-Goetz M 2017 Assembly of embryonic and extraembryonic stem cells to mimic embryogenesis in vitro Science 356 eaal1810 10.1126/science.aal1810 28254784

상세보기
31 Sato T Stange DE Ferrante M Vries RG Van Es JH Van den Brink S Van Houdt WJ Pronk A Van Gorp J Siersema PD Clevers H 2011 Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium Gastroenterology 141 1762 1772 10.1053/j.gastro.2011.07.050 21889923

상세보기
32 Barker N Huch M Kujala P van de Wetering M Snippert HJ van Es JH Sato T Stange DE Begthel H van den Born M Danenberg E van den Brink S Korving J Abo A Peters PJ Wright N Poulsom R Clevers H 2010 Lgr5(＋ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro Cell Stem Cell 6 25 36 10.1016/j.stem.2009.11.013 20085740

상세보기
33 Jung KB Lee H Son YS Lee MO Kim YD Oh SJ Kwon O Cho S Cho HS Kim DS Oh JH Zilbauer M Min JK Jung CR Kim J Son MY 2018 Interleukin-2 induces the in vitro maturation of human pluripotent stem cell-derived intestinal organoids Nat Commun 9 3039 10.1038/s41467-018-05450-8 30072687

상세보기
34 McCracken KW Aihara E Martin B Crawford CM Broda T Treguier J Zhang X Shannon JM Montrose MH Wells JM 2017 Wnt/β-catenin promotes gastric fundus specification in mice and humans Nature 541 182 187 10.1038/nature21021 28052057

상세보기
35 Múnera JO Sundaram N Rankin SA Hill D Watson C Mahe M Vallance JE Shroyer NF Sinagoga KL Zarzoso-Lacoste A Hudson JR Howell JC Chatuvedi P Spence JR Shannon JM Zorn AM Helmrath MA Wells JM 2017 Differentiation of human pluripotent stem cells into colonic organoids via transient activation of BMP signaling Cell Stem Cell 21 51 64.e6 10.1016/j.stem.2017.05.020 28648364

상세보기
36 Chichagova V Hilgen G Ghareeb A Georgiou M Carter M Sernagor E Lako M Armstrong L 2020 Human iPSC differentiation to retinal organoids in response to IGF1 and BMP4 activation is line- and method-dependent Stem Cells 38 195 201 10.1002/stem.3116 31721366

상세보기
37 Cruz-Acuña R Quirós M Farkas AE Dedhia PH Huang S Siuda D García-Hernández V Miller AJ Spence JR Nusrat A García AJ 2017 Synthetic hydrogels for human intestinal organoid generation and colonic wound repair Nat Cell Biol 19 1326 1335 10.1038/ncb3632 29058719

상세보기
38 Sachs N Tsukamoto Y Kujala P Peters PJ Clevers H 2017 Intestinal epithelial organoids fuse to form self-organizing tubes in floating collagen gels Development 144 1107 1112 10.1242/dev.143933 28292848

상세보기
39 Giobbe GG Crowley C Luni C Campinoti S Khedr M Kretzschmar K De Santis MM Zambaiti E Michielin F Meran L Hu Q van Son G Urbani L Manfredi A Giomo M Eaton S Cacchiarelli D Li VSW Clevers H Bonfanti P Elvassore N De Coppi P 2019 Extracellular matrix hydrogel derived from decellularized tissues enables endodermal organoid culture Nat Commun 10 5658 10.1038/s41467-019-13605-4 31827102

상세보기
40 Kumar SV Er PX Lawlor KT Motazedian A Scurr M Ghobrial I Combes AN Zappia L Oshlack A Stanley EG Little MH 2019 Kidney micro-organoids in suspension culture as a scalable source of human pluripotent stem cell-derived kidney cells Development 146 dev172361 10.1242/dev.172361 30846463

상세보기
41 DiStefano T Chen HY Panebianco C Kaya KD Brooks MJ Gieser L Morgan NY Pohida T Swaroop A 2018 Accelerated and improved differentiation of retinal organoids from pluripotent stem cells in rotating-wall vessel bioreactors Stem Cell Reports 10 300 313 10.1016/j.stemcr.2017.11.001 29233554

상세보기
42 Muguruma K Nishiyama A Kawakami H Hashimoto K Sasai Y 2015 Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells Cell Rep 10 537 550 10.1016/j.celrep.2014.12.051 25640179

상세보기
43 Giandomenico SL Mierau SB Gibbons GM Wenger LMD Masullo L Sit T Sutcliffe M Boulanger J Tripodi M Derivery E Paulsen O Lakatos A Lancaster MA 2019 Cerebral organoids at the air-liquid interface generate diverse nerve tracts with functional output Nat Neurosci 22 669 679 10.1038/s41593-019-0350-2 30886407

상세보기
44 Upadhyay S Palmberg L 2018 Air-liquid interface: relevant in vitro models for investigating air pollutant-induced pulmonary toxicity Toxicol Sci 164 21 30 10.1093/toxsci/kfy053 29534242

상세보기
45 Takasato M Er PX Chiu HS Little MH 2016 Generation of kidney organoids from human pluripotent stem cells Nat Protoc 11 1681 1692 10.1038/nprot.2016.098 27560173

상세보기
46 Watanabe M Buth JE Vishlaghi N de la Torre-Ubieta L Taxidis J Khakh BS Coppola G Pearson CA Yamauchi K Gong D Dai X Damoiseaux R Aliyari R Liebscher S Schenke-Layland K Caneda C Huang EJ Zhang Y Cheng G Geschwind DH Golshani P Sun R Novitch BG 2017 Self-organized cerebral organoids with human-specific features predict effective drugs to combat Zika virus infection Cell Rep 21 517 532 10.1016/j.celrep.2017.09.047 29020636

상세보기
47 Qian X Nguyen HN Song MM Hadiono C Ogden SC Hammack C Yao B Hamersky GR Jacob F Zhong C Yoon KJ Jeang W Lin L Li Y Thakor J Berg DA Zhang C Kang E Chickering M Nauen D Ho CY Wen Z Christian KM Shi PY Maher BJ Wu H Jin P Tang H Song H Ming GL 2016 Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure Cell 165 1238 1254 10.1016/j.cell.2016.04.032 27118425

상세보기
48 Kim H Xu R Padmashri R Dunaevsky A Liu Y Dreyfus CF Jiang P 2019 Pluripotent stem cell-derived cerebral organoids reveal human oligodendrogenesis with dorsal and ventral origins Stem Cell Reports 12 890 905 10.1016/j.stemcr.2019.04.011 31091434

상세보기
49 Pellegrini L Bonfio C Chadwick J Begum F Skehel M Lancaster MA 2020 Human CNS barrier-forming organoids with cerebrospinal fluid production Science 369 eaaz5626 10.1126/science.aaz5626 32527923

상세보기
50 Susaimanickam PJ Maddileti S Pulimamidi VK Boyinpally SR Naik RR Naik MN Reddy GB Sangwan VS Mariappan I 2017 Generating minicorneal organoids from human induced pluripotent stem cells Development 144 2338 2351 10.1242/dev.143040 28559289

상세보기
51 Low JH Li P Chew EGY Zhou B Suzuki K Zhang T Lian MM Liu M Aizawa E Rodriguez Esteban C Yong KSM Chen Q Campistol JM Fang M Khor CC Foo JN Izpisua Belmonte JC Xia Y 2019 Generation of human PSC-derived kidney organoids with patterned nephron segments and a de novo vascular network Cell Stem Cell 25 373 387.e9 10.1016/j.stem.2019.06.009 31303547

상세보기
52 Workman MJ Mahe MM Trisno S Poling HM Watson CL Sundaram N Chang CF Schiesser J Aubert P Stanley EG Elefanty AG Miyaoka Y Mandegar MA Conklin BR Neunlist M Brugmann SA Helmrath MA Wells JM 2017 Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system Nat Med 23 49 59 10.1038/nm.4233 27869805

상세보기
53 Jung KB Lee H Son YS Lee JH Cho HS Lee MO Oh JH Lee J Kim S Jung CR Kim J Son MY 2018 In vitro and in vivo imaging and tracking of intestinal organoids from human induced pluripotent stem cells FASEB J 32 111 122 10.1096/fj.201700504r 28855280

상세보기
54 Mithal A Capilla A Heinze D Berical A Villacorta- Martin C Vedaie M Jacob A Abo K Szymaniak A Peasley M Stuffer A Mahoney J Kotton DN Hawkins F Mostoslavsky G 2020 Generation of mesenchyme free intestinal organoids from human induced pluripotent stem cells Nat Commun 11 215 10.1038/s41467-019-13916-6 31924806

상세보기
55 Tao T Wang Y Chen W Li Z Su W Guo Y Deng P Qin J 2019 Engineering human islet organoids from iPSCs using an organ-on-chip platform Lab Chip 19 948 958 10.1039/C8LC01298A 30719525

상세보기
56 Asai A Aihara E Watson C Mourya R Mizuochi T Shivakumar P Phelan K Mayhew C Helmrath M Takebe T Wells J Bezerra JA 2017 Paracrine signals regulate human liver organoid maturation from induced pluripotent stem cells Development 144 1056 1064 10.1242/dev.142794 28275009

상세보기
57 Miller AJ Dye BR Ferrer-Torres D Hill DR Overeem AW Shea LD Spence JR 2019 Generation of lung organoids from human pluripotent stem cells in vitro Nat Protoc 14 518 540 10.1038/s41596-018-0104-8 30664680

상세보기
58 Koike H Iwasawa K Ouchi R Maezawa M Giesbrecht K Saiki N Ferguson A Kimura M Thompson WL Wells JM Zorn AM Takebe T 2019 Modelling human hepato-biliary-pancreatic organogenesis from the foregut-midgut boundary Nature 574 112 116 10.1038/s41586-019-1598-0 31554966

상세보기
59 Lee H Son YS Lee MO Ryu JW Park K Kwon O Jung KB Kim K Ryu TY Baek A Kim J Jung CR Ryu CM Park YJ Han TS Kim DS Cho HS Son MY 2020 Low-dose interleukin-2 alleviates dextran sodium sulfate-induced colitis in mice by recovering intestinal integrity and inhibiting AKT-dependent pathways Theranostics 10 5048 5063 10.7150/thno.41534 32308767

상세보기
60 Paşca SP 2019 Assembling human brain organoids Science 363 126 127 10.1126/science.aau5729 30630918

상세보기
61 Watson CL Mahe MM Múnera J Howell JC Sundaram N Poling HM Schweitzer JI Vallance JE Mayhew CN Sun Y Grabowski G Finkbeiner SR Spence JR Shroyer NF Wells JM Helmrath MA 2014 An in vivo model of human small intestine using pluripotent stem cells Nat Med 20 1310 1314 10.1038/nm.3737 25326803

상세보기
62 Cortez AR Poling HM Brown NE Singh A Mahe MM Helmrath MA 2018 Transplantation of human intestinal organoids into the mouse mesentery: a more physiologic and anatomic engraftment site Surgery 164 643 650 10.1016/j.surg.2018.04.048 30072255

상세보기
63 Mansour AA Gonçalves JT Bloyd CW Li H Fernandes S Quang D Johnston S Parylak SL Jin X Gage FH 2018 An in vivo model of functional and vascularized human brain organoids Nat Biotechnol 36 432 441 10.1038/nbt.4127 29658944

상세보기
64 Hill J Cave J 2015 Targeting the vasculature to improve neural progenitor transplant survival Transl Neurosci 6 162 167 10.1515/tnsci-2015-0016 28123800

상세보기
65 Takebe T Wells JM 2019 Organoids by design Science 364 956 959 10.1126/science.aaw7567 31171692

상세보기
66 Czerniecki SM Cruz NM Harder JL Menon R Annis J Otto EA Gulieva RE Islas LV Kim YK Tran LM Martins TJ Pippin JW Fu H Kretzler M Shankland SJ Himmelfarb J Moon RT Paragas N Freedman BS 2018 High- throughput screening enhances kidney organoid differentiation from human pluripotent stem cells and enables automated multidimensional phenotyping Cell Stem Cell 22 929 940.e4 10.1016/j.stem.2018.04.022 29779890

상세보기
67 Crespo M Vilar E Tsai SY Chang K Amin S Srinivasan T Zhang T Pipalia NH Chen HJ Witherspoon M Gordillo M Xiang JZ Maxfield FR Lipkin S Evans T Chen S 2017 Colonic organoids derived from human induced pluripotent stem cells for modeling colorectal cancer and drug testing Nat Med 23 878 884 10.1038/nm.4355 28628110

상세보기
68 Tocchio A Tamplenizza M Martello F Gerges I Rossi E Argentiere S Rodighiero S Zhao W Milani P Lenardi C 2015 Versatile fabrication of vascularizable scaffolds for large tissue engineering in bioreactor Biomaterials 45 124 131 10.1016/j.biomaterials.2014.12.031 25662502

상세보기
69 Wang Y Gunasekara DB Reed MI DiSalvo M Bultman SJ Sims CE Magness ST Allbritton NL 2017 A microen-gineered collagen scaffold for generating a polarized crypt- villus architecture of human small intestinal epithelium Biomaterials 128 44 55 10.1016/j.biomaterials.2017.03.005 28288348

상세보기
70 Nikolaev M Mitrofanova O Broguiere N Geraldo S Dutta D Tabata Y Elci B Brandenberg N Kolotuev I Gjorevski N Clevers H Lutolf MP 2020 Homeostatic mini-intestines through scaffold-guided organoid morphogenesis Nature 585 574 578 10.1038/s41586-020-2724-8 32939089

상세보기
71 McKinnon DD Brown TE Kyburz KA Kiyotake E Anseth KS 2014 Design and characterization of a synthetically accessible, photodegradable hydrogel for user-directed formation of neural networks Biomacromolecules 15 2808 2816 10.1021/bm500731b 24932668

상세보기
72 Sarig-Nadir O Livnat N Zajdman R Shoham S Seliktar D 2009 Laser photoablation of guidance microchannels into hydrogels directs cell growth in three dimensions Biophys J 96 4743 4752 10.1016/j.bpj.2009.03.019 19486697

상세보기
73 Zhu W Qu X Zhu J Ma X Patel S Liu J Wang P Lai CS Gou M Xu Y Zhang K Chen S 2017 Direct 3D bioprinting of prevascularized tissue constructs with complex microarchitecture Biomaterials 124 106 115 10.1016/j.biomaterials.2017.01.042 28192772

상세보기
74 Demers CJ Soundararajan P Chennampally P Cox GA Briscoe J Collins SD Smith RL 2016 Development-on-chip: in vitro neural tube patterning with a microfluidic device Development 143 1884 1892 10.1242/dev.126847 27246712

상세보기
75 Fabre KM Livingston C Tagle DA 2014 Organs-on-chips (microphysiological systems): tools to expedite efficacy and toxicity testing in human tissue Exp Biol Med (Maywood) 239 1073 1077 10.1177/1535370214538916 24962171

상세보기
76 Zhang C Zhao Z Abdul Rahim NA van Noort D Yu H 2009 Towards a human-on-chip: culturing multiple cell types on a chip with compartmentalized microenvironments Lab Chip 9 3185 3192 10.1039/b915147h 19865724

상세보기
77 Ronaldson-Bouchard K Vunjak-Novakovic G 2018 Organs-on-a- chip: a fast track for engineered human tissues in drug development Cell Stem Cell 22 310 324 10.1016/j.stem.2018.02.011 29499151

상세보기
78 Peterson LW Artis D 2014 Intestinal epithelial cells: regulators of barrier function and immune homeostasis Nat Rev Immunol 14 141 153 10.1038/nri3608 24566914

상세보기
79 Erkosar B Storelli G Mitchell M Bozonnet L Bozonnet N Leulier F 2015 Pathogen virulence impedes mutualist-mediated enhancement of host juvenile growth via inhibition of protein digestion Cell Host Microbe 18 445 455 10.1016/j.chom.2015.09.001 26439865

상세보기
80 Cho I Yamanishi S Cox L Methé BA Zavadil J Li K Gao Z Mahana D Raju K Teitler I Li H Alekseyenko AV Blaser MJ 2012 Antibiotics in early life alter the murine colonic microbiome and adiposity Nature 488 621 626 10.1038/nature11400 22914093

상세보기
81 Hviid A Svanström H Frisch M 2011 Antibiotic use and inflammatory bowel diseases in childhood Gut 60 49 54 10.1136/gut.2010.219683 20966024

상세보기
82 Diaz Heijtz R Wang S Anuar F Qian Y Björkholm B Samuelsson A Hibberd ML Forssberg H Pettersson S 2011 Normal gut microbiota modulates brain development and behavior Proc Natl Acad Sci U S A 108 3047 3052 10.1073/pnas.1010529108 21282636

상세보기
83 Leslie JL Huang S Opp JS Nagy MS Kobayashi M Young VB Spence JR 2015 Persistence and toxin production by Clostridium difficile within human intestinal organoids result in disruption of epithelial paracellular barrier function Infect Immun 83 138 145 10.1128/IAI.02561-14 25312952

상세보기
84 Son YS Ki SJ Thanavel R Kim JJ Lee MO Kim J Jung CR Han TS Cho HS Ryu CM Kim SH Park DS Son MY 2020 Maturation of human intestinal organoids in vitro facilitates colonization by commensal lactobacilli by reinforcing the mucus layer FASEB J [Epub ahead of print] 10.1096/fj.202000063R 32602623

상세보기
85 Vatanen T Plichta DR Somani J Münch PC Arthur TD Hall AB Rudolf S Oakeley EJ Ke X Young RA Haiser HJ Kolde R Yassour M Luopajärvi K Siljander H Virtanen SM Ilonen J Uibo R Tillmann V Mokurov S Dorshakova N Porter JA McHardy AC Lähdesmäki H Vlamakis H Huttenhower C Knip M Xavier RJ 2019 Genomic variation and strain-specific functional adaptation in the human gut microbiome during early life Nat Microbiol 4 470 479 10.1038/s41564-018-0321-5 30559407

상세보기
86 Forbester JL Goulding D Vallier L Hannan N Hale C Pickard D Mukhopadhyay S Dougan G 2015 Interaction of Salmonella enterica serovar Typhimurium with intestinal organoids derived from human induced pluripotent stem cells Infect Immun 83 2926 2934 10.1128/IAI.00161-15 25964470

상세보기
87 Taguchi A Kaku Y Ohmori T Sharmin S Ogawa M Sasaki H Nishinakamura R 2014 Redefining the in vivo origin of metanephric nephron progenitors enables generation of complex kidney structures from pluripotent stem cells Cell Stem Cell 14 53 67 10.1016/j.stem.2013.11.010 24332837

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88 Mandai M Fujii M Hashiguchi T Sunagawa GA Ito SI Sun J Kaneko J Sho J Yamada C Takahashi M 2017 iPSC-derived retina transplants improve vision in rd1 end-stage retinal-degeneration mice Stem Cell Reports 8 69 83 10.1016/j.stemcr.2016.12.008 28076757

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89 Mariani J Coppola G Zhang P Abyzov A Provini L Tomasini L Amenduni M Szekely A Palejev D Wilson M Gerstein M Grigorenko EL Chawarska K Pelphrey KA Howe JR Vaccarino FM 2015 FOXG1-dependent dysregulation of GABA/glutamate neuron differentiation in autism spectrum disorders Cell 162 375 390 10.1016/j.cell.2015.06.034 26186191

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90 Lindeboom RG van Voorthuijsen L Oost KC Rodríguez- Colman MJ Luna-Velez MV Furlan C Baraille F Jansen PW Ribeiro A Burgering BM Snippert HJ Vermeulen M 2018 Integrative multi-omics analysis of intestinal organoid differentiation Mol Syst Biol 14 e8227 10.15252/msb.20188227 29945941

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활용도 Top5 논문

해당 논문의 주제분야에서 활용도가 높은 상위 5개 콘텐츠를 보여줍니다.
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표제어: PCR

동의어: Packet Collision Rate

용어 설명 출처 목록 (6)

용어 설명: PCR은 세균 특이성이 있는 primer를 이용하여 적은 수의 세균이 있을지라도 쉽게 검출할 수 있는 유용한 방법이며, 이를 이용하여 구강 내 치면세균막이나 타액에서 직접 세균을 검출할 수 있게 되었다[8].

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구성항목	기본정보 상세정보 관리번호, 논문명, 저널/프로시딩명, 저자 , 발행년, 권, 호, 시작페이지, 끝페이지, 발행기관 관리번호, 논문명, 대등논문명, 저자 , 저널/프로시딩명, 발행기관, 발행년, 발행언어, 권, 호, 시작페이지, 끝페이지, ISBN, ISSN, 주제분야, 키워드, 초록(한글), 초록(영문), 저자(소속기관)
저장형식	Text(ASCII format) Excel format RefWorks Direct Export RIS format (for Reference Manager, ProCite, EndNote), Scholar's Aids, Mendeley
메일정보	받는사람 (필수) @ 보내는사람 (선택) @ 제목 내용 KISTI 검색결과 이메일 서비스
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