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Structurally graduated collagen scaffolds applied to the ex vivo generation of platelets from human pluripotent stem cell-derived megakaryocytes: Enhancing production and purity.

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cam.issuedOnline2018-08-08
datacite.issupplementedby.urlhttps://doi.org/10.17863/CAM.26141
dc.contributor.authorShepherd, Jennifer H
dc.contributor.authorHoward, Daniel
dc.contributor.authorWaller, Amie K
dc.contributor.authorFoster, Holly Rebecca
dc.contributor.authorMueller, Annett
dc.contributor.authorMoreau, Thomas
dc.contributor.authorEvans, Amanda L
dc.contributor.authorArumugam, Meera
dc.contributor.authorBouët Chalon, Guénaëlle
dc.contributor.authorVriend, Eleonora
dc.contributor.authorDavidenko, Natalia
dc.contributor.authorGhevaert, Cedric
dc.contributor.authorBest, Serena M
dc.contributor.authorCameron, Ruth E
dc.contributor.orcidWaller, Amie [0000-0002-9726-5560]
dc.contributor.orcidMoreau, Thomas [0000-0003-1090-6685]
dc.contributor.orcidGhevaert, Cedric [0000-0002-9251-0934]
dc.contributor.orcidBest, Serena [0000-0001-7866-8607]
dc.contributor.orcidCameron, Ruth [0000-0003-1573-4923]
dc.date.accessioned2018-11-09T00:30:24Z
dc.date.available2018-11-09T00:30:24Z
dc.date.issued2018-11
dc.description.abstractPlatelet transfusions are a key treatment option for a range of life threatening conditions including cancer, chemotherapy and surgery. Efficient ex vivo systems to generate donor independent platelets in clinically relevant numbers could provide a useful substitute. Large quantities of megakaryocytes (MKs) can be produced from human pluripotent stem cells, but in 2D culture the ratio of platelets harvested from MK cells has been limited and restricts production rate. The development of biomaterial cell supports that replicate vital hematopoietic micro-environment cues are one strategy that may increase in vitro platelet production rates from iPS derived Megakaryocyte cells. In this paper, we present the results obtained generating, simulating and using a novel structurally-graded collagen scaffold within a flow bioreactor system seeded with programmed stem cells. Theoretical analysis of porosity using micro-computed tomography analysis and synthetic micro-particle filtration provided a predictive tool to tailor cell distribution throughout the material. When used with MK programmed stem cells the graded scaffolds influenced cell location while maintaining the ability to continuously release metabolically active CD41 + CD42 + functional platelets. This scaffold design and novel fabrication technique offers a significant advance in understanding the influence of scaffold architectures on cell seeding, retention and platelet production.
dc.description.sponsorshipThis work was supported by the European Research Council [ERC Advanced Grant 320598 3D-E], EPSRC grant EP/N019938/1 and grants from the NHS Blood and Transplant, the Medical Research Council (MR/L022982/1) and the European Union (SilkFusion: AMD-767309-3).
dc.format.mediumPrint-Electronic
dc.identifier.doi10.17863/CAM.32251
dc.identifier.eissn1878-5905
dc.identifier.issn0142-9612
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/284878
dc.languageeng
dc.language.isoeng
dc.publisherElsevier BV
dc.publisher.urlhttp://dx.doi.org/10.1016/j.biomaterials.2018.08.019
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectBioreactor
dc.subjectBone marrow model
dc.subjectCollagen
dc.subjectDepth straining
dc.subjectForward programming
dc.subjectHuman induced pluripotent stem cells
dc.subjectInterconnectivity
dc.subjectMegakaryocytes
dc.subjectParallel flow membrane filter
dc.subjectPlatelets
dc.subjectScaffold architecture
dc.subjectSettling zones
dc.subjectShear flow
dc.subjectBiocompatible Materials
dc.subjectBioreactors
dc.subjectBlood Platelets
dc.subjectCell Culture Techniques
dc.subjectCells, Cultured
dc.subjectCollagen
dc.subjectEquipment Design
dc.subjectHumans
dc.subjectMegakaryocytes
dc.subjectPluripotent Stem Cells
dc.subjectThrombopoiesis
dc.subjectTissue Scaffolds
dc.titleStructurally graduated collagen scaffolds applied to the ex vivo generation of platelets from human pluripotent stem cell-derived megakaryocytes: Enhancing production and purity.
dc.typeArticle
dcterms.dateAccepted2018-08-06
prism.endingPage144
prism.publicationDate2018
prism.publicationNameBiomaterials
prism.startingPage135
prism.volume182
pubs.funder-project-idEuropean Research Council (320598)
pubs.funder-project-idMedical Research Council (MR/L022982/1)
pubs.funder-project-idEngineering and Physical Sciences Research Council (EP/N019938/1)
pubs.funder-project-idMedical Research Council (MC_PC_12009)
pubs.funder-project-idMRC (MC_PC_14116 v2)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Future and Emerging Technologies (FET) (767309)
rioxxterms.licenseref.startdate2018-11
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionAM
rioxxterms.versionofrecord10.1016/j.biomaterials.2018.08.019

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