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Effects of amotosalen treatment on human platelet lysate bioactivity: A proof-of-concept study

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dc.contributor Háskóli Íslands
dc.contributor University of Iceland
dc.contributor Háskólinn í Reykjavík
dc.contributor Reykjavik University
dc.contributor.author Christensen, Christian
dc.contributor.author Jonsdottir-Buch, Sandra Mjoll
dc.contributor.author Sigurjonsson, Olafur
dc.date.accessioned 2021-01-18T14:54:02Z
dc.date.available 2021-01-18T14:54:02Z
dc.date.issued 2020-04-15
dc.identifier.citation Christensen C, Jonsdottir-Buch SM, Sigurjonsson OE (2020) Effects of amotosalen treatment on human platelet lysate bioactivity: A proof-of-concept study. PLoS ONE 15(4): e0220163. https://doi.org/10.1371/journal.pone.0220163
dc.identifier.issn 1932-6203
dc.identifier.uri https://hdl.handle.net/20.500.11815/2389
dc.description Publisher's version (útgefin grein)
dc.description.abstract Background Clinical application of mesenchymal stromal cells (MSCs) usually requires an in vitro expansion step to reach clinically relevant numbers. In vitro cell expansion necessitates supplementation of basal mammalian cell culture medium with growth factors. To avoid using supplements containing animal substances, human platelet lysates (hPL) produced from expired and pathogen inactivated platelet concentrates can be used in place of fetal bovine serum. However, globally, most transfusion units are currently not pathogen inactivated. As blood banks are the sole source of platelet concentrates for hPL production, it is important to ensure product safety and standardized production methods. In this proof-of-concept study we assessed the feasibility of producing hPL from expired platelet concentrates with pathogen inactivation applied after platelet lysis by evaluating the retention of growth factors, cytokines, and the ability to support MSC proliferation and tri-lineage differentiation. Methodology/Principal findings Bone marrow-derived MSCs (BM-MSCs) were expanded and differentiated using hPL derived from pathogen inactivated platelet lysates (hPL-PIPL), with pathogen inactivation by amotosalen/ultraviolet A treatment applied after lysis of expired platelets. Results were compared to those using hPL produced from conventional expired pathogen inactivated platelet concentrates (hPL-PIPC), with pathogen inactivation applied after blood donation. hPL-PIPL treatment had lower concentrations of soluble growth factors and cytokines than hPL-PIPC treatment. When used as supplementation in cell culture, BM-MSCs proliferated at a reduced rate, but more consistently, in hPL-PIPL than in hPL-PIPC. The ability to support tri-lineage differentiation was comparable between lysates. Conclusion/Significance These results suggest that functional hPL can be produced from expired and untreated platelet lysates by applying pathogen inactivation after platelet lysis. When carried out post-expiration, pathogen inactivation may provide a valuable solution for further standardizing global hPL production methods, increasing the pool of starting material, and meeting future demand for animal-free supplements in human cell culturing.
dc.description.sponsorship The funder provided support in the form of salaries for authors [SMJ], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.
dc.format.extent e0220163
dc.language.iso en
dc.publisher Public Library of Science (PLoS)
dc.relation.ispartofseries PLOS ONE;15(4)
dc.rights info:eu-repo/semantics/openAccess
dc.subject Platelets
dc.subject Cell differentiation
dc.subject Cell cultures
dc.subject Growth factors
dc.subject Frumurannsóknir
dc.title Effects of amotosalen treatment on human platelet lysate bioactivity: A proof-of-concept study
dc.type info:eu-repo/semantics/article
dcterms.license This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.description.version Peer Reviewed
dc.identifier.journal Plos One
dc.identifier.doi 10.1371/journal.pone.0220163
dc.relation.url https://dx.plos.org/10.1371/journal.pone.0220163
dc.contributor.department Læknadeild (HÍ)
dc.contributor.department Faculty of Medicine (UI)
dc.contributor.school Heilbrigðisvísindasvið (HÍ)
dc.contributor.school School of Health Sciences (UI)
dc.contributor.school Tæknisvið (HR)
dc.contributor.school School of Technology (RU)

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