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Review

Acute radiation syndrome drug discovery using organ-on-chip platforms

ORCID Icon &
Pages 865-878 | Received 17 Feb 2022, Accepted 06 Jul 2022, Published online: 18 Jul 2022

References

  • Ma C, Peng Y, Li H, et al. Organ-on-a-chip: a new paradigm for drug development. Trends Pharmacol Sci. 2021;42:119–133.
  • Shanti A, Teo J, Stefanini C. In vitro immune organs-on-chip for drug development: a review. Pharmaceutics. 2018;10:278.
  • Torisawa YS, Tung YC. Editorial for the special issue on organs-on-chips. Micromachines (Basel). 2020;11:369.
  • Bissell MJ, Ewald A. Goodbye flat biology - time for the 3rd and the 4th dimensions. J Cell Sci. 2017;130:3–5.
  • Khademhosseini A, Langer R. A decade of progress in tissue engineering. Nat Protoc. 2016;11:1775–1781.
  • Chen CS. 3D biomimetic cultures: the next platform for cell biology. Trends Cell Biol. 2016;26:798–800.
  • Ma C, Witkowski MT, Harris J, et al. Leukemia-on-a-chip: dissecting the chemoresistance mechanisms in B cell acute lymphoblastic leukemia bone marrow niche. Sci Adv. 2020;6. DOI:10.1126/sciadv.aba5536.
  • Prantil-Baun R, Novak R, Das D, et al. Physiologically based pharmacokinetic and pharmacodynamic analysis enabled by microfluidically linked organs-on-chips. Annu Rev Pharmacol Toxicol. 2018;58:37–64.
  • Quan Y, Sun M, Tan Z, et al. Organ-on-a-chip: the next generation platform for risk assessment of radiobiology. RSC Adv. 2020;10:39521–39530.
  • Torisawa YS, Spina CS, Mammoto T, et al. Bone marrow-on-a-chip replicates hematopoietic niche physiology in vitro. Nat Methods. 2014;11:663–669.
  • Torisawa YS, Mammoto T, Jiang E, et al. Modeling hematopoiesis and responses to radiation countermeasures in a bone marrow-on-a-chip. Tissue Eng Part C Methods. 2016;22:509–515.
  • Singh VK, Newman VL, Berg AN, et al. Animal models for acute radiation syndrome drug discovery. Expert Opin Drug Discov. 2015;10:497–517.
  • Singh VK, Olabisi AO. Nonhuman primates as models for the discovery and development of radiation countermeasures. Expert Opin Drug Discov. 2017;12:695–709.
  • Williams JP, Jackson IL, Shah JR, et al. Animal models and medical countermeasures development for radiation-induced lung damage: report from an NIAID workshop. Radiat Res. 2012;177:e0025–39.
  • Williams JP, Brown SL, Georges GE, et al. Animal models for medical countermeasures to radiation exposure. Radiat Res. 2010;173:557–578.
  • Hasegawa A, Tanigawa K, Ohtsuru A, et al. Health effects of radiation and other health problems in the aftermath of nuclear accidents, with an emphasis on Fukushima. Lancet. 2015;386:479–488.
  • Marzaleh MA, Rezaee R, Rezaianzadeh A, et al. Design and validation of a hospital emergency department preparedness questionnaire for radiation accidents, nuclear accidents, and nuclear terrorism in Iran. Am J Disaster Med. 2020;15:283–292.
  • MacVittie TJ, Farese AM, Jackson WE 3rd. A systematic review of the Hematopoietic Acute Radiation Syndrome (H-ARS) in canines and non-human primates: acute mixed neutron/gamma vs. reference quality radiations. Health Phys. 2020;119:527–558.
  • Singh VK, Seed TM. A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: part I. Radiation sub-syndromes, animal models and FDA-approved countermeasures. Int J Radiat Biol. 2017;93:851–869.
  • Girgis M, Li Y, Jayatilake M, et al. Short-term metabolic disruptions in urine of mouse models following exposure to low doses of oxygen ion radiation. J Environ Sci Health C Toxicol Carcinog. 2021; 39: 234–249.
  • Li Y, Girgis M, Wise SY, et al. Analysis of the metabolomic profile in serum of irradiated nonhuman primates treated with Ex-Rad, a radiation countermeasure. Sci Rep. 2021;11:11449.
  • Dissmore T, DeMarco AG, Jayatilake M, et al. Longitudinal metabolic alterations in plasma of rats exposed to low doses of high linear energy transfer radiation. J Environ Sci Health C Toxicol Carcinog. 2021; 39: 219–233.
  • Girgis M, Li Y, Ma J, et al. Comparative proteomic analysis of serum from nonhuman primates administered BIO 300: a promising radiation countermeasure. Sci Rep. 2020;10:19343.
  • Hall EJ, Giaccia AJ. Radiobiology for the radiobiologist. 7th ed. Philadelphia: Lippincott Williams and Wilkins; 2012.
  • Stewart FA, Akleyev AV, Hauer-Jensen M, et al. ICRP publication 118: ICRP statement on tissue reactions and early and late effects of radiation in normal tissues and organs–threshold doses for tissue reactions in a radiation protection context. Ann ICRP. 2012;41:1–322.
  • Seed TM. Acute effects. The Health Risks of Extraterrestrial Environments; 2011 [cited 2021 Jul 20]. Available from: https://three.jsc.nasa.gov/articles/SeedAcuteEffects.pdf
  • Jalili-Firoozinezhad S, Prantil-Baun R, Jiang A, et al. Modeling radiation injury-induced cell death and countermeasure drug responses in a human gut-on-a-chip. Cell Death Dis. 2018;9:223.
  • Frohlich E. Issues with cancer spheroid models in therapeutic drug screening. Curr Pharm Des. 2020;26:2137–2148.
  • Tung YC, Hsiao AY, Allen SG, et al. High-throughput 3D spheroid culture and drug testing using a 384 hanging drop array. Analyst. 2011;136:473–478.
  • Timm DM, Chen J, Sing D, et al. A high-throughput three-dimensional cell migration assay for toxicity screening with mobile device-based macroscopic image analysis. Sci Rep. 2013;3:3000.
  • Devarasetty M, Mazzocchi AR, Skardal A. Applications of bioengineered 3D tissue and tumor organoids in drug development and precision medicine: current and future. Biodrugs. 2018;32:53–68.
  • In JG, Foulke-Abel J, Estes MK, et al. Human mini-guts: new insights into intestinal physiology and host-pathogen interactions. Nat Rev Gastroenterol Hepatol. 2016;13:633–642.
  • Fujii M, Matano M, Toshimitsu K, et al. Human intestinal organoids maintain self-renewal capacity and cellular diversity in niche-inspired culture condition. Cell Stem Cell. 2018;23:787–93 e6.
  • Kim J, Koo BK, Knoblich JA. Human organoids: model systems for human biology and medicine. Nat Rev Mol Cell Biol. 2020;21:571–584.
  • Rowe RG, Daley GQ. Induced pluripotent stem cells in disease modelling and drug discovery. Nat Rev Genet. 2019;20:377–388.
  • Whitesides GM. The origins and the future of microfluidics. Nature. 2006;442:368–373.
  • Haeberle S, Zengerle R. Microfluidic platforms for lab-on-a-chip applications. Lab Chip. 2007;7:1094–1110.
  • World Econmic Forum. Top Ten Emerging Technologies. 2016 [cited 2022 Jan 22]. Available from: https://www.weforum.org/agenda/2016/06/top-10-emerging-technologies-2016
  • Sano E, Mori C, Matsuoka N, et al. Tetrafluoroethylene-propylene elastomer for fabrication of microfluidic organs-on-chips resistant to drug absorption. Micromachines (Basel). 2019;10. DOI:10.3390/mi10110793.
  • Morrison SJ, Scadden DT. The bone marrow niche for haematopoietic stem cells. Nature. 2014;505:327–334.
  • Sugiyama T, Nagasawa T. Bone marrow niches for hematopoietic stem cells and immune cells. Inflamm Allergy Drug Targets. 2012;11:201–206.
  • Yu VW, Scadden DT. Hematopoietic stem cell and its bone marrow niche. Curr Top Dev Biol. 2016;118:21–44.
  • Dexter TM, Allen TD, Lajtha LG. Conditions controlling the proliferation of haemopoietic stem cells in vitro. J Cell Physiol. 1977;91:335–344.
  • Dexter TM, Coutinho LH, Spooncer E, et al. Stromal cells in haemopoiesis. Ciba Found Symp. 1990;148:76–86. discussion 86-95.
  • Laver J, Ebell W, Castro-Malaspina H. Radiobiological properties of the human hematopoietic microenvironment: contrasting sensitivities of proliferative capacity and hematopoietic function to in vitro irradiation. Blood. 1986;67:1090–1097.
  • Sieber S, Wirth L, Cavak N, et al. Bone marrow-on-a-chip: long-term culture of human haematopoietic stem cells in a three-dimensional microfluidic environment. J Tissue Eng Regen Med. 2018;12:479–489.
  • Bruce A, Evans R, Mezan R, et al. Three-dimensional microfluidic tri-culture model of the bone marrow microenvironment for study of acute lymphoblastic leukemia. PLoS One. 2015;10:e0140506.
  • Chou DB, Frismantas V, Milton Y, et al. On-chip recapitulation of clinical bone marrow toxicities and patient-specific pathophysiology. Nat Biomed Eng. 2020;4:394–406.
  • McDermott AJ, Huffnagle GB. The microbiome and regulation of mucosal immunity. Immunology. 2014;142:24–31.
  • Bein A, Shin W, Jalili-Firoozinezhad S, et al. Microfluidic organ-on-a-chip models of human intestine. Cell Mol Gastroenterol Hepatol. 2018;5:659–668.
  • Xiang Y, Wen H, Yu Y, et al. Gut-on-chip: recreating human intestine in vitro. J Tissue Eng. 2020;11:2041731420965318.
  • Shah P, Fritz JV, Glaab E, et al. A microfluidics-based in vitro model of the gastrointestinal human-microbe interface. Nat Commun. 2016;7:11535.
  • Shim KY, Lee D, Han J, et al. Microfluidic gut-on-a-chip with three-dimensional villi structure. Biomed Microdevices. 2017;19:37.
  • Kim HJ, Li H, Collins JJ, et al. Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip. Proc Natl Acad Sci U S A. 2016;113:E7–15.
  • Hollingsworth BA, Cassatt DR, DiCarlo AL, et al. Acute radiation syndrome and the microbiome: impact and review. Front Pharmacol. 2021;12:643283.
  • Jalili-Firoozinezhad S, Gazzaniga FS, Calamari EL, et al. A complex human gut microbiome cultured in an anaerobic intestine-on-a-chip. Nat Biomed Eng. 2019;3:520–531.
  • Tovaglieri A, Sontheimer-Phelps A, Geirnaert A, et al. Species-specific enhancement of enterohemorrhagic E. coli pathogenesis mediated by microbiome metabolites. Microbiome. 2019;7:43.
  • Cheema AK, Li Y, and Singh J, et al. Microbiome study in irradiated mice treated with BIO 300, a promising radiation countermeasure. Anim Microbiome. 2021;3:71.
  • Ingber DE. Human organs-on-chips for disease modelling, drug development and personalized medicine. Nat Rev Genet. 2022. DOI:10.1038/s41576-022-00466-9
  • Peter RU, Gottlober P, Nadeshina N, et al. Radiation lentigo. A distinct cutaneous lesion after accidental radiation exposure. Arch Dermatol. 1997;133:209–211.
  • Peter RU, Gottlober P. Management of cutaneous radiation injuries: diagnostic and therapeutic principles of the cutaneous radiation syndrome. Mil Med. 2002;167:110–112.
  • Lataillade JJ, Doucet C, Bey E, et al. New approach to radiation burn treatment by dosimetry-guided surgery combined with autologous mesenchymal stem cell therapy. Regen Med. 2007;2:785–794.
  • O’Neill AT, Monteiro-Riviere NA, Walker GM. Characterization of microfluidic human epidermal keratinocyte culture. Cytotechnology. 2008;56:197–207.
  • Abaci HE, Gledhill K, Guo Z, et al. Pumpless microfluidic platform for drug testing on human skin equivalents. Lab Chip. 2015;15:882–888.
  • Mori N, Morimoto Y, Takeuchi S. Skin integrated with perfusable vascular channels on a chip. Biomaterials. 2017;116:48–56.
  • Ramadan Q, Ting FC. In vitro micro-physiological immune-competent model of the human skin. Lab Chip. 2016;16:1899–1908.
  • Bovard D, Iskandar A, Luettich K, et al. Organs-on-a-chip: a new paradigm for toxicological assessment and preclinical drug development. Toxicol Res Appl. 2017;1:1–16.
  • Munoz-Schuffenegger P, Ng S, Dawson LA. Radiation-induced liver toxicity. Semin Radiat Oncol. 2017;27(4):350–357.
  • Nakajima T, Ninomiya Y, Nenoi M. Radiation-induced reactions in the liver - Modulation of radiation effects by lifestyle-related factors. Int J Mol Sci. 2018;19:3855.
  • Ware BR, Khetani SR. Engineered liver platforms for different phases of drug development. Trends Biotechnol. 2017;35:172–183.
  • Bhise NS, Manoharan V, Massa S, et al. A liver-on-a-chip platform with bioprinted hepatic spheroids. Biofabrication. 2016;8:014101.
  • Bavli D, Prill S, Ezra E, et al. Real-time monitoring of metabolic function in liver-on-chip microdevices tracks the dynamics of mitochondrial dysfunction. Proc Natl Acad Sci USA. 2016;113:E2231–40.
  • Ong LJY, Chong LH, Jin L, et al. A pump-free microfluidic 3D perfusion platform for the efficient differentiation of human hepatocyte-like cells. Biotechnol Bioeng. 2017;114:2360–2370.
  • Ju SM, Jang HJ, Kim KB, et al. High-throughput cytotoxicity testing system of Acetaminophen using a microfluidic device (MFD) in HepG2 cells. J Toxicol Environ Health. 2015;78:1063–1072.
  • Ramaiahgari SC, den Braver MW, Herpers B, et al. A 3D in vitro model of differentiated HepG2 cell spheroids with improved liver-like properties for repeated dose high-throughput toxicity studies. Arch Toxicol. 2014;88:1083–1095.
  • Takahashi Y, Hori Y, Yamamoto T, et al. 3D spheroid cultures improve the metabolic gene expression profiles of HepaRG cells. Biosci Rep. 2015;35:e00208.
  • Snyder JE, Hamid Q, Wang C, et al. Bioprinting cell-laden matrigel for radioprotection study of liver by pro-drug conversion in a dual-tissue microfluidic chip. Biofabrication. 2011;3:034112.
  • Kniazeva T, Hsiao JC, Charest JL, et al. A microfluidic respiratory assist device with high gas permeance for artificial lung applications. Biomed Microdevices. 2011;13:315–323.
  • Huh D, Matthews BD, Mammoto A, et al. Reconstituting organ-level lung functions on a chip. Science. 2010;328:1662–1668.
  • Stucki AO, Stucki JD, Hall SR, et al. A lung-on-a-chip array with an integrated bio-inspired respiration mechanism. Lab Chip. 2015;15:1302–1310.
  • Venkatesulu BP, Mahadevan LS, Aliru ML, et al. Radiation-induced endothelial vascular injury: a review of possible mechanisms. JACC Basic Transl Sci. 2018;3:563–572.
  • Jain A, Barrile R, van der Meer AD, et al. Primary human lung alveolus-on-a-chip model of intravascular thrombosis for assessment of therapeutics. Clin Pharmacol Ther. 2018;103:332–340.
  • Millet LJ, Giannone RJ, Greenwood MS, et al. Identifying candidate biomarkers of ionizing radiation in human pulmonary microvascular lumens using microfluidics-a pilot study. Micromachines (Basel). 2021;12. DOI:10.3390/mi12080904.
  • Dauth S, Maoz BM, Sheehy SP, et al. Neurons derived from different brain regions are inherently different in vitro: a novel multiregional brain-on-a-chip. J Neurophysiol. 2017;117:1320–1341.
  • Stiles J, Jernigan TL. The basics of brain development. Neuropsychol Rev. 2010;20:327–348.
  • Oberheim NA, Takano T, Han X, et al. Uniquely hominid features of adult human astrocytes. J Neurosci. 2009;29:3276–3287.
  • Yamada M, Mimori Y, Kasagi F, et al. Incidence of dementia, Alzheimer disease, and vascular dementia in a Japanese population: radiation effects research foundation adult health study. Neuroepidemiology. 2008;30:152–160.
  • Riudavets MA, Mena H, Bouffard JP, et al. Relationship between radiation injury and Alzheimer-related neurodegenerative changes. Clin Neuropathol. 2005;24:236–238.
  • Gijzen L, Marescotti D, Raineri E, et al. An intestine-on-a-chip model of plug-and-play modularity to study inflammatory processes. SLAS Technol. 2020;25:585–597.
  • Esch EW, Bahinski A, Huh D. Organs-on-chips at the frontiers of drug discovery. Nat Rev Drug Discov. 2015;14:248–260.
  • Peters MF, Choy AL, Pin C, et al. Developing in vitro assays to transform gastrointestinal safety assessment: potential for microphysiological systems. Lab Chip. 2020;20:1177–1190.
  • Abbott NJ. Astrocyte-endothelial interactions and blood-brain barrier permeability. J Anat. 2002;200:629–638.
  • Cho H, Seo JH, Wong KH, et al. Three-dimensional blood-brain barrier model for in vitro studies of neurovascular pathology. Sci Rep. 2015;5:15222.
  • Xu H, Li Z, Yu Y, et al. A dynamic in vivo-like organotypic blood-brain barrier model to probe metastatic brain tumors. Sci Rep. 2016;6:36670.
  • Baradaran-Ghahfarokhi M. Radiation-induced kidney injury. J Renal Injury Prev. 2012;1:49–50.
  • Naughton CA. Drug-induced nephrotoxicity. Am Fam Physician. 2008;78:743–750.
  • Justice BA, Badr NA, Felder RA. 3D cell culture opens new dimensions in cell-based assays. Drug Discov Today. 2009;14:102–107.
  • Hoenig MP, Zeidel ML. Homeostasis, the milieu interieur, and the wisdom of the nephron. Clin J Am Soc Nephrol. 2014;9:1272–1281.
  • Homan KA, Kolesky DB, Skylar-Scott MA, et al. Bioprinting of 3D convoluted renal proximal tubules on perfusable chips. Sci Rep. 2016;6:34845.
  • Sochol RD, Gupta NR, Bonventre JV. A role for 3D printing in kidney-on-a-chip platforms. Curr Transplant Rep. 2016;3:82–92.
  • Taunk NK, Haffty BG, Kostis JB, et al. Radiation-induced heart disease: pathologic abnormalities and putative mechanisms. Front Oncol. 2015;5:39.
  • Darby SC, Cutter DJ, Boerma M, et al. Radiation-related heart disease: current knowledge and future prospects. Int J Radiat Oncol Biol Phys. 2010;76:656–665.
  • Agarwal A, Goss JA, Cho A, et al. Microfluidic heart on a chip for higher throughput pharmacological studies. Lab Chip. 2013;13:3599–3608.
  • Balachandran K, Alford PW, Wylie-Sears J, et al. Cyclic strain induces dual-mode endothelial-mesenchymal transformation of the cardiac valve. Proc Natl Acad Sci USA. 2011;108:19943–19948.
  • Park J, Wetzel I, and Dreau D, et al. 3D miniaturization of human organs for drug discovery. Adv Healthc Mater. 2018;7:1700551.
  • Vernetti LA, Vogt A, Gough A, et al. Evolution of experimental models of the liver to predict human drug hepatotoxicity and efficacy. Clin Liver Dis. 2017;21:197–214.
  • Wagner I, Materne EM, Brincker S, et al. A dynamic multi-organ-chip for long-term cultivation and substance testing proven by 3D human liver and skin tissue co-culture. Lab Chip. 2013;13:3538–3547.
  • Materne EM, Ramme AP, Terrasso AP, et al. A multi-organ chip co-culture of neurospheres and liver equivalents for long-term substance testing. J Biotechnol. 2015;205:36–46.
  • Choe A, Ha SK, Choi I, et al. Microfluidic Gut-liver chip for reproducing the first pass metabolism. Biomed Microdevices. 2017;19:4.
  • Castell JV, Donato MT, Gomez-Lechon MJ. Metabolism and bioactivation of toxicants in the lung. The in vitro cellular approach. Exp Toxicol Pathol. 2005;57(Suppl 1):189–204.
  • Coppeta JR, Mescher MJ, Isenberg BC, et al. A portable and reconfigurable multi-organ platform for drug development with onboard microfluidic flow control. Lab Chip. 2016;17:134–144.
  • Frey O, Misun PM, Fluri DA, et al. Reconfigurable microfluidic hanging drop network for multi-tissue interaction and analysis. Nat Commun. 2014;5:4250.
  • Maschmeyer I, Lorenz AK, Schimek K, et al. A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents. Lab Chip. 2015;15:2688–2699.
  • Oleaga C, Bernabini C, Smith AS, et al. Multi-Organ toxicity demonstration in a functional human in vitro system composed of four organs. Sci Rep. 2016;6:20030.
  • U.S. Food and Drug Administration. Guidance document: product development under the animal rule; 2015 [cited 2020 Oct 20]. Available from: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm399217.pdf.
  • Witkowski MT, Dolgalev I, Evensen NA, et al. Extensive remodeling of the immune microenvironment in B cell acute lymphoblastic leukemia. Cancer Cell. 2020;37:867–82 e12.
  • Marturano-Kruik A, Nava MM, Yeager K, et al. Human bone perivascular niche-on-a-chip for studying metastatic colonization. Proc Natl Acad Sci U S A. 2018;115:1256–1261.
  • Beir V. Mechanisms of radiation-induced cancer. Health risks from exposure to low levels of ionizing radiation. Washington: The National Academies Press; 1980.
  • Low LA, and Tagle DA. Organs-on-chips: progress, challenges, and future directions. Experimental biology and medicine. Exp Biol Med. 2017;242:1573–1578.
  • Oye KA, Eichler HG, Hoos A, et al. Pharmaceuticals licensing and reimbursement in the European Union, United States, and Japan. Clin Pharmacol Ther. 2016;100:626–632.
  • Langhans SA. Using 3D in vitro cell culture models in anti-cancer drug discovery. Expert Opin Drug Discov. 2021;16:841–850.
  • Moysidou CM, Owens RM. Advances in modelling the human microbiome-gut-brain axis in vitro. Biochem Soc Trans. 2021;49:187–201.