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dc.contributor.authorChou, David
dc.contributor.authorFrismantas, Viktoras
dc.contributor.authorMilton, Yuka
dc.contributor.authorDavid, Rhiannon
dc.contributor.authorPop-Damkov, Petar
dc.contributor.authorFerguson, Douglas
dc.contributor.authorMacDonald, Alexander
dc.contributor.authorVargel Bolukbasi, Ozge
dc.contributor.authorJoyce, Cailin E.
dc.contributor.authorMoreira Teixeira, Liliana S.
dc.contributor.authorRech, Arianna
dc.contributor.authorJiang, Amanda
dc.contributor.authorCalamari, Elizabeth
dc.contributor.authorJalili-Firoozinezhad, Sasan
dc.contributor.authorFurlong, Brooke
dc.contributor.authorO’Sullivan, Lucy R.
dc.contributor.authorNg, Carlos F.
dc.contributor.authorChoe, Youngjae
dc.contributor.authorMarquez, Susan
dc.contributor.authorMyers, Kasiani C.
dc.contributor.authorWeinberg, Olga K.
dc.contributor.authorHasserjian, Robert
dc.contributor.authorNovak, Richard
dc.contributor.authorLevy, Oren
dc.contributor.authorPrantil-Baun, Rachelle
dc.contributor.authorNovina, Carl
dc.contributor.authorShimamura, Akiko
dc.contributor.authorEwart, Lorna
dc.contributor.authorIngber, Donald
dc.date.accessioned2022-03-11T15:27:47Z
dc.date.issued2020-01-27
dc.identifier.citationChou, David, Viktoras Frismantas, Yuka Milton, Rhiannon David, Petar Pop-Damkov, Douglas Ferguson, Alexander MacDonald et al. "On-chip recapitulation of clinical bone marrow toxicities and patient-specific pathophysiology." Nature Biomedical Engineering 4, no. 4 (2020): 394-406. DOI: 10.1038/s41551-019-0495-z
dc.identifier.issn2157-846Xen_US
dc.identifier.urihttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37370981*
dc.description.abstractThe inaccessibility of living bone marrow hampers the study of its pathophysiology under myelotoxic stress induced by drugs, radiation or genetic mutations. Here, we show that a vascularized human bone-marrow-on-a-chip supports the differentiation and maturation of multiple blood-cell lineages over 4 weeks while improving CD34+ cell maintenance, and that it recapitulates aspects of marrow injury, including myeloerythroid toxicity after clinically relevant exposures to chemotherapeutic drugs and ionizing radiation as well as marrow recovery after drug-induced myelosuppression. The chip comprises a fluidic channel filled with a fibrin gel in which CD34+ cells and bone-marrow-derived stromal cells are co-cultured, a parallel channel lined by human vascular endothelium and perfused with culture medium, and a porous membrane separating the two channels. We also show that bone-marrow chips containing cells from patients with the rare genetic disorder Shwachman–Diamond syndrome reproduced key haematopoietic defects and led to the discovery of a neutrophil-maturation abnormality. As an in vitro model of haematopoietic dysfunction, the bone-marrow-on-a-chip may serve as a human-specific alternative to animal testing for the study of bone-marrow pathophysiology.en_US
dc.language.isoen_USen_US
dc.publisherSpringer Science and Business Media LLCen_US
dc.relationNature Biomedical Engineeringen_US
dc.relation.isversionofdoi:10.1038/s41551-019-0495-zen_US
dc.relation.hasversionhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160021/en_US
dash.licenseMETA_ONLY
dc.subjectComputer Science Applicationsen_US
dc.subjectBiomedical Engineeringen_US
dc.subjectMedicine (miscellaneous)en_US
dc.subjectBioengineeringen_US
dc.subjectBiotechnologyen_US
dc.titleOn-chip recapitulation of clinical bone marrow toxicities and patient-specific pathophysiologyen_US
dc.typeJournal Articleen_US
dc.description.versionAccepted Manuscripten_US
dc.relation.journalNature Biomedical Engineeringen_US
dash.depositing.authorIngber, Donald
dash.waiver2019-11-12
dc.date.available2022-03-11T15:27:47Z
dash.affiliation.otherHarvard Medical Schoolen_US
dc.identifier.doi10.1038/s41551-019-0495-z
dash.source.volume4en_US
dash.source.page394-406en_US
dash.source.issue4en_US
dash.contributor.affiliatedFurlong, Brooke
dash.contributor.affiliatedCalamari, Elizabeth
dash.contributor.affiliatedVargel Bolukbasi, Ozge
dash.contributor.affiliatedFrismantas, Viktoras
dash.contributor.affiliatedMarquez, Susan
dash.contributor.affiliatedChou, David
dash.contributor.affiliatedChoe, Youngjae
dash.contributor.affiliatedLevy, Oren
dash.contributor.affiliatedJiang, Amanda
dash.contributor.affiliatedHasserjian, Robert
dash.contributor.affiliatedNovina, Carl
dash.contributor.affiliatedNovak, Richard
dash.contributor.affiliatedIngber, Donald
dash.contributor.affiliatedShimamura, Akiko


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