Is It Time to Start Transitioning From 2D to 3D Cell Culture?

Frontiers in Molecular Biosciences, Journal Year: 2020, Volume and Issue: 7

Published: March 6, 2020

Cell culture is an important and necessary process in drug discovery, cancer research, as well stem cell research. Most cells are currently cultured using two-dimensional (2D) methods, but new improved methods that implement three-dimensional (3D) techniques suggest compelling evidence much more advanced experiments can be performed. When performing 3D experiments, the environment manipulated to mimic of a vivo provide accurate data about cell-to-cell interactions, tumor characteristics, metabolic profiling, other types diseases. Scaffold based such hydrogel-based support, polymeric hard material-based hydrophilic glass fiber, organoids employed, each provides its own advantages applications. Likewise, there also scaffold-free used hanging drop microplates, magnetic levitation, spheroid microplates with ultra-low attachment coating. has potential alternative ways study organ behavior via use expected eventually bridge gap between 2D animal models. The present review compares culture, details surrounding different techniques, focuses on future applications culture.

Language: Английский

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Human organs-on-chips for disease modelling, drug development and personalized medicine

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 23(8), P. 467 - 491

Published: March 25, 2022

The failure of animal models to predict therapeutic responses in humans is a major problem that also brings into question their use for basic research. Organ-on-a-chip (organ chip) microfluidic devices lined with living cells cultured under fluid flow can recapitulate organ-level physiology and pathophysiology high fidelity. Here, I review how single multiple human organ chip systems have been used model complex diseases rare genetic disorders, study host–microbiome interactions, whole-body inter-organ reproduce clinical drugs, radiation, toxins infectious pathogens. address the challenges must be overcome chips accepted by pharmaceutical industry regulatory agencies, as well discuss recent advances field. It evident instead drug development avatars personalized medicine ever closer realization. This Review discusses types organ-on-a-chip diverse applications disease modelling, medicine, reach full potential.

Language: Английский

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Engineering organoids

Nature Reviews Materials, Journal Year: 2021, Volume and Issue: 6(5), P. 402 - 420

Published: Feb. 19, 2021

Language: Английский

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Modelling cancer in microfluidic human organs-on-chips

Nature reviews. Cancer, Journal Year: 2019, Volume and Issue: 19(2), P. 65 - 81

Published: Jan. 15, 2019

Language: Английский

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Organs-on-chips: into the next decade

Nature Reviews Drug Discovery, Journal Year: 2020, Volume and Issue: 20(5), P. 345 - 361

Published: Sept. 10, 2020

Language: Английский

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A complex human gut microbiome cultured in an anaerobic intestine-on-a-chip

Nature Biomedical Engineering, Journal Year: 2019, Volume and Issue: 3(7), P. 520 - 531

Published: May 13, 2019

Language: Английский

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Organ-on-a-chip: recent breakthroughs and future prospects

BioMedical Engineering OnLine, Journal Year: 2020, Volume and Issue: 19(1)

Published: Feb. 12, 2020

Abstract The organ-on-a-chip (OOAC) is in the list of top 10 emerging technologies and refers to a physiological organ biomimetic system built on microfluidic chip. Through combination cell biology, engineering, biomaterial technology, microenvironment chip simulates that terms tissue interfaces mechanical stimulation. This reflects structural functional characteristics human can predict response an array stimuli including drug responses environmental effects. OOAC has broad applications precision medicine biological defense strategies. Here, we introduce concepts review its application construction models, development, toxicology from perspective different organs. We further discuss existing challenges provide future perspectives for application.

Language: Английский

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Homeostatic mini-intestines through scaffold-guided organoid morphogenesis

Nature, Journal Year: 2020, Volume and Issue: 585(7826), P. 574 - 578

Published: Sept. 16, 2020

Language: Английский

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Microfluidic Organ-on-a-Chip Models of Human Intestine

Cellular and Molecular Gastroenterology and Hepatology, Journal Year: 2018, Volume and Issue: 5(4), P. 659 - 668

Published: Jan. 1, 2018

Microfluidic organ-on-a-chip models of human intestine have been developed and used to study intestinal physiology pathophysiology. In this article, we review field describe how microfluidic Intestine Chips offer new capabilities not possible with conventional culture systems or organoid cultures, including the ability analyze contributions individual cellular, chemical, physical control parameters one-at-a-time; coculture cells commensal microbiome for extended times; create human-relevant disease models. We also discuss potential future applications Chips, they might be drug development personalized medicine. SummaryOrgans-on-chips are cell that recapitulate structure, function, physiology, pathology living organs in vitro. recent various intestine-on-a-chip their value modeling, discovery, Organs-on-chips The major organ function is carry out digestion, absorption, secretion, motility,1Silverthorn D.U. Ober W.C. Garrison C.W. Silverthorn A.C. Johnson B.R. Human physiology: an integrated approach. Pearson/Benjamin Cummings, San Francisco2009Google Scholar addition establishing a protective epithelial barrier between digestive environment body. addition, intestines regulate systemic by metabolizing drugs2Benet L.Z. Wu C.-Y. Hebert M.F. Wacher V.J. Intestinal metabolism antitransport processes: paradigm shift oral delivery.J Control Release. 1996; 39: 139-143Crossref Scopus (188) Google Scholar; communicate other organs, such as liver3Moore F.A. Moore E.E. Poggetti R. McAnena O.J. Peterson V.M. Abernathy C.M. Parsons P.E. Gut bacterial translocation via portal vein: clinical perspective torso trauma.J Trauma Acute Care Surg. 1991; 31: 629-638Crossref (447) Scholar, 4Bloemen J.G. Venema K. van de Poll M.C. Damink S.W.O. Buurman W.A. Dejong C.H. Short chain fatty acids exchange across gut liver humans measured at surgery.Clin Nutr. 2009; 28: 657-661Abstract Full Text PDF PubMed (217) pancreas,5Ahuja M. Schwartz D.M. Tandon Son A. Zeng Swaim W. Eckhaus Hoffman V. Cui Y. Xiao B. Orai1-mediated antimicrobial secretion from pancreatic acini shapes regulates innate immunity.Cell Metab. 2017; 25: 635-646Abstract (84) flow; contain enteric nervous system forms part gut-brain axis.6Cryan J.F. Dinan T.G. Mind-altering microorganisms: impact microbiota on brain behaviour.Nat Rev Neurosci. 2012; 13: 701-712Crossref (2487) 7Mayer E.A. feelings: emerging biology gut–brain communication.Nat 2011; 12: 453-466Crossref (986) site which microbes live interact lymphoid tissues host immune system, contributes significantly homeostasis.8Garrett W.S. Gordon J.I. Glimcher L.H. Homeostasis inflammation intestine.Cell. 2010; 140: 859-870Abstract (556) 9Round J.L. Mazmanian S.K. responses during health disease.Nat Immunol. 9: 313-323Crossref (3250) For example, its metabolites (eg, short-chain acids) recently shown play central role maintenance health, modulation, both enteral nonenteral diseases.10Wong J.M. De Souza Kendall Emam Jenkins D.J. Colonic health: fermentation short acids.J Clin Gastroenterol. 2006; 40: 235-243Crossref (1832) 11Smith P.M. Howitt M.R. Panikov N. Michaud Gallini C.A. Bohlooly-y Glickman J.N. Garrett microbial metabolites, acids, colonic Treg homeostasis.Science. 2013; 341: 569-573Crossref (3048) However, analysis interactions has limited genetic metagenomics because it these epithelium more than about 1 day using even sophisticated cultures. Thus, there great efforts develop experimental vitro ex vivo permit pathophysiology presence absence microbiome. most common model absorption involve culturing established line Caco-212Hidalgo I.J. Raub T.J. Borchardt R.T. Characterization colon carcinoma (Caco-2) permeability.Gastroenterology. 1989; 96: 736-749Abstract (1952) 13Artursson P. Karlsson J. Correlation apparent permeability coefficients cells.Biochem Biophys Res Commun. 175: 880-885Crossref (1674) HT-2914Pinto M.G.V. Gómez Seifert S. Watzl Holzapfel W.H. Franz Lactobacilli stimulate response modulate TLR expression HT29 vitro.Int J Food Microbiol. 133: 86-93Crossref (113) 15Eveillard Fourel Bare Kernéis Coconnier M.H. Karjalainen T. Bourlioux Servin A.L. Identification characterization adhesive factors Clostridium difficile involved adhesion enterocyte-like Caco-2 mucus-secreting culture.Mol 1993; 7: 371-381Crossref (74) cells) extracellular matrix (ECM)-coated, porous membranes within Transwell insert devices. Although commonly pharmaceutical industry, 2-dimensional (2D) format fails physiological 3-dimensional (3D) tissue morphology re-establish key differentiated functions mucus production, villi formation, cytochrome P-450-based metabolism).16Kim H.J. Huh D. Hamilton G. Ingber D.E. gut-on-a-chip inhabited flora experiences peristalsis-like motions flow.Lab Chip. 2165-2174Crossref (1046) 17Kim Gut-on-a-Chip microenvironment induces undergo villus differentiation.Integr Biol. 5: 1130-1140Crossref (443) These static cannot support cells, critical physiology,16Kim bacteria rapidly overgrow contaminate cultures day. Several models, everted sac18Alam M.A. Al-Jenoobi F.I. Al-mohizea A.M. Everted sac tool research: limitations applications.J Pharm Pharmacol. 64: 326-336Crossref (131) Ussing chamber,19Rozehnal Nakai Hoepner U. Fischer Kamiyama E. Takahashi Yasuda Mueller small mounted chamber characterizing drugs.European Journal Pharmaceutical Sciences. 46: 367-373Crossref (104) 20Smith Mirabelli C. Fondacaro Ryan F. Dent 5-fluorouracil absorption: Use chambers assess transport metabolism.Pharm Res. 1988; 598-603Crossref (45) assays; however, expected lifespan (<8 hours) sufficient enable many studies normal clinically relevant host-microbiome crosstalk. had technically challenging primary 3D derived either crypts containing endogenous induced pluripotent stem revolutionized maintaining niches supporting differentiation subtypes vitro.21Sato Van Es J.H. Snippert Stange Vries R.G. Den Born Barker Shroyer N.F. Wetering Clevers H. Paneth constitute niche Lgr5 crypts.Nature. 469: 415-418Crossref (1723) 22Jung Sato Merlos-Suárez Barriga F.M. Iglesias Rossell Auer Gallardo Blasco Sancho Isolation expansion cells.Nat Med. 17: 1225-1227Crossref (497) When cultured ECM gel medium Wnt, R-spondin, noggin, growth factors, organoids (enteroids) spontaneously villus-crypt morphologic organization histogenesis.22Jung Each biopsy patient can grown, frozen, revived multiple reuses, potentially establish biobanks23van Francies H.E. Francis Bounova Iorio Pronk Houdt Gorp Taylor-Weiner Kester L. Prospective derivation biobank colorectal cancer patients.Cell. 2015; 161: 933-945Abstract (1348) 24Sato SnapShot: growing cells.Cell. 1700-1700.e1Abstract (97) multiplexed screening platforms validating candidates advance medicine.25Fatehullah Tan S.H. Organoids Cell 2016; 18: 246-254Crossref (837) lack types found intestine, endothelium-lined blood vessels important transport, pharmacokinetic (PK) analysis, modeling. They do experience fluid flows cyclic mechanical deformations similar those experienced peristalsing contribute function. Furthermore, each enteroid closed lumen when surrounding gel, experimentally difficult sample manipulate luminal components nutrients, drugs, toxins). This structure limits researchers PK, metabolism), interactions.26Park G.-S. Park Shin Zhao Sheikh Oh S.J. Kim Emulating ecosystem gastrointestinal tract vitro.Stem Rep. 321-334Crossref (43) challenges overcome Organ Chip intestine. devices, originally fabricated methods adapted computer microchip manufacturing soft lithography), continuously perfused arranged simulate tissue- organ-level physiology.27Bhatia S.N. organs-on-chips.Nat Biotechnol. 2014; 32: 760-772Crossref (1976) Over past 5 years, engineered increasing complexity include neighboring channels lined microvascular endothelium, microbes, pathogenic bacteria, some application forces mimic (Figure 1). Next emulate (Table Also considered implications work complex development, medicine future.Table 1Design Characteristics ModelsModelTEERAbsorptionCocultureMicrobiomeDifferentiationPeristalsisDrug metabolismCrypt-villus axisOxygen modulationDisease modelingStatic TranswellYes12Hidalgo ScholarYes12Hidalgo ScholarNoYes14Pinto (<24 h)NoNoNoNoNoNo OrganoidNoYes95Zietek Rath Haller Daniel assessing nutrient sensing incretin secretion.Sci 16831Crossref ScholarNoYes96Zhang Y.G. Xia Sun Salmonella-infected crypt-derived host–bacterial interactions.Physiol 2: e12147Crossref (150) (<1 h)Yes21Sato ScholarNoYes97Lu Rettenmeier Paszek Yueh M.-F. Tukey R.H. Trottier Barbier O. Chen Crypt cytotoxicity studies.Drug Metab Dispos. 45: 748-754Crossref (28) ScholarYes21Sato ScholarNoYes22Jung Ex vivoYes19Rozehnal 98Madsen Cornish Soper McKaigney Jijon Yachimec Doyle Jewell Simone Probiotic enhance murine function.Gastroenterology. 2001; 121: 580-591Abstract (890) ScholarYes19Rozehnal (<3 h)Yes19Rozehnal ScholarNoYes100Sjöberg Å. Lutz Tannergren Wingolf Borde Ungell A.-L. Comprehensive regional prediction fraction absorbed drugs technique.Eur Sci. 48: 166-180Crossref (151) ScholarYes99Worton Candy Wallis Clarke Osborne Haddon Stephen Studies early association Salmonella typhimurium mucosa vitro: relationship virulence.J Med 29: 283-294Crossref (31) ScholarYes98Madsen ScaffoldNoNoNoNoYes40Wang Gunasekara D.B. Reed M.I. DiSalvo Bultman Sims C.E. Magness S.T. Allbritton N.L. A microengineered collagen scaffold generating polarized crypt-villus architecture epithelium.Biomaterials. 128: 44-55Crossref (191) ScholarNoNoYes40Wang ScholarNoNoMicrofluidic 2-channelYes32Maoz B.M. Herland Henry O.Y.F. Leineweber Yadid Mannix Kujala Fitzgerald Parker K.K. combined multi-electrode array transepithelial electrical resistance measurement capabilities.Lab 2294-2302Crossref ScholarYes30Gao Liu Lin J.-M. Wang Jiang monolayers mass spectrometry membrane-based device.Lab 978-985Crossref (94) ScholarYes37Esch M.B. Mahler G.J. Stokol Shuler M.L. Body-on-a-chip simulation suggests ingested nanoparticles cause injury.Lab 14: 3081-3092Crossref ScholarNoNoNoYes39Shim K.-Y. Lee Han Nguyen N.-T. Sung three-dimensional structure.Biomed Microdevices. 19: 37Crossref (120) ScholarYes39Shim ScholarNoNo vivoNoYes99Worton ScholarNoNoYes101Dawson Dyer Macfie Davies Karsai Greenman Jacobsen chip based full thickness dual flow.Biomicrofluidics. 10: 064101Crossref (32) ScholarNoYes101Dawson Multichannel (HuMiX)Yes41Shah Fritz J.V. Glaab Desai M.S. Greenhalgh Frachet Niegowska Estes Jäger Seguin-Devaux microfluidics-based human–microbe interface.Nat 11535Crossref (326) ScholarNoNoYes41Shah h)NoNoNoNoYes41Shah ScholarNo ChipYes16Kim 42Kim Li Collins J.J. Contributions deformation overgrowth gut-on-a-chip.Proc Natl Acad 113: E7-E15Crossref (549) ScholarYes16Kim ScholarNoYes16Kim (>7 d)Yes17Kim ScholarNoYes42Kim ScholarTEER, resistance. Open table tab TEER, devices hollow microchannels less mm width laminar flow nanoliter microliter scale volumes, thus, amenable use cells. By syringe peristaltic pump, may desired rates through microchannel, dynamic ranges associated shear stresses surface observed lumen,28Vickerman Blundo Chung Kamm Design, fabrication implementation novel multi-parameter platform real-time imaging.Lab 2008; 8: 1468-1477Crossref (294) 29Tanaka Yamato Okano Kitamori Evaluation effects stress hepatocytes microchip-based system.Meas Sci Technol. 3167-3170Crossref (87) capillaries. fluidic enables delivery compounds, toxins grown highly regulated spatiotemporal manner. Most 2 separated porous, ECM-coated polyester polycarbonate membrane, immortalized surfaces.30Gao monolayer formed device c

Language: Английский

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Reproducing human and cross-species drug toxicities using a Liver-Chip

Science Translational Medicine, Journal Year: 2019, Volume and Issue: 11(517)

Published: Nov. 6, 2019

A rat, dog, and human Liver-Chip designed using microengineered Organs-on-Chips technology recapitulates species-specific drug toxicities.

Language: Английский

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