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dc.contributor.authorMorris, TJen
dc.contributor.authorPicken, Aen
dc.contributor.authorSharp, DMCen
dc.contributor.authorSlater, Nigelen
dc.contributor.authorHewitt, CJen
dc.contributor.authorCoopman, Ken
dc.date.accessioned2017-02-22T14:08:31Z
dc.date.available2017-02-22T14:08:31Z
dc.date.issued2016-12-01en
dc.identifier.issn0011-2240
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/262708
dc.description.abstractWith the cell therapy industry continuing to grow, the ability to preserve clinical grade cells, including mesenchymal stem cells (MSCs), whilst retaining cell viability and function remains critical for the generation of off-the-shelf therapies. Cryopreservation of MSCs, using slow freezing, is an established process at lab scale. However, the cytotoxicity of cryoprotectants, like Me$_{2}$SO, raises questions about the impact of prolonged cell exposure to cryoprotectant at temperatures >0 °C during processing of large cell batches for allogenic therapies prior to rapid cooling in a controlled rate freezer or in the clinic prior to administration. Here we show that exposure of human bone marrow derived MSCs to Me$_{2}$SO for ≥1 h before freezing, or after thawing, degrades membrane integrity, short-term cell attachment efficiency and alters cell immunophenotype. After 2 h's exposure to Me$_{2}$SO at 37 °C post-thaw, membrane integrity dropped to ∼70% and only ∼50% of cells retained the ability to adhere to tissue culture plastic. Furthermore, only 70% of the recovered MSCs retained an immunophenotype consistent with the ISCT minimal criteria after exposure. We also saw a similar loss of membrane integrity and attachment efficiency after exposing osteoblast (HOS TE85) cells to Me$_{2}$SO before, and after, cryopreservation. Overall, these results show that freezing medium exposure is a critical determinant of product quality as process scale increases. Defining and reporting cell sensitivity to freezing medium exposure, both before and after cryopreservation, enables a fair judgement of how scalable a particular cryopreservation process can be, and consequently whether the therapy has commercial feasibility.
dc.description.sponsorshipThe authors would like to acknowledge the Engineering and Physical Sciences Research Council (EPSRC; UK, EP/F500491/1) and Bioprocessing Research Industry Club (BBSRC/BRIC; UK, BB/I017602/1) for their support and funding.
dc.languageengen
dc.language.isoenen
dc.publisherElsevier
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjecthuman mesenchymal stem cellsen
dc.subjectHOS TE85en
dc.subjectcryopreservationen
dc.subjectdimethylsulfoxideen
dc.subjectbioprocessingen
dc.subjecttoxicityen
dc.titleThe effect of Me$_{2}$SO overexposure during cryopreservation on HOS TE85 and hMSC viability, growth and qualityen
dc.typeArticle
prism.endingPage375
prism.issueIdentifier3en
prism.publicationDate2016en
prism.publicationNameCryobiologyen
prism.startingPage367
prism.volume73en
dc.identifier.doi10.17863/CAM.7994
dcterms.dateAccepted2016-09-19en
rioxxterms.versionofrecord10.1016/j.cryobiol.2016.09.004en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2016-12-01en
dc.contributor.orcidSlater, Nigel [0000-0002-0207-9440]
dc.identifier.eissn1090-2392
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBBSRC (BB/I016961/1)
cam.issuedOnline2016-09-20en
cam.orpheus.successThu Jan 30 12:56:48 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International