Cargando…

Pathogen reduction through additive-free short-wave UV light irradiation retains the optimal efficacy of human platelet lysate for the expansion of human bone marrow mesenchymal stem cells

BACKGROUND: We recently developed and characterized a standardized and clinical grade human Platelet Lysate (hPL) that constitutes an advantageous substitute for fetal bovine serum (FBS) for human mesenchymal stem cell (hMSC) expansion required in cell therapy procedures, avoiding xenogenic risks (v...

Descripción completa

Detalles Bibliográficos
Autores principales: Viau, Sabrina, Chabrand, Lucie, Eap, Sandy, Lorant, Judith, Rouger, Karl, Goudaliez, Francis, Sumian, Chryslain, Delorme, Bruno
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538655/
https://www.ncbi.nlm.nih.gov/pubmed/28763452
http://dx.doi.org/10.1371/journal.pone.0181406
_version_ 1783254379999002624
author Viau, Sabrina
Chabrand, Lucie
Eap, Sandy
Lorant, Judith
Rouger, Karl
Goudaliez, Francis
Sumian, Chryslain
Delorme, Bruno
author_facet Viau, Sabrina
Chabrand, Lucie
Eap, Sandy
Lorant, Judith
Rouger, Karl
Goudaliez, Francis
Sumian, Chryslain
Delorme, Bruno
author_sort Viau, Sabrina
collection PubMed
description BACKGROUND: We recently developed and characterized a standardized and clinical grade human Platelet Lysate (hPL) that constitutes an advantageous substitute for fetal bovine serum (FBS) for human mesenchymal stem cell (hMSC) expansion required in cell therapy procedures, avoiding xenogenic risks (virological and immunological) and ethical issues. Because of the progressive use of pathogen-reduced (PR) labile blood components, and the requirement of ensuring the viral safety of raw materials for cell therapy products, we evaluated the impact of the novel procedure known as THERAFLEX UV-Platelets for pathogen reduction on hPL quality (growth factors content) and efficacy (as a medium supplement for hMSC expansion). This technology is based on short-wave ultraviolet light (UV-C) that induces non-reversible damages in DNA and RNA of pathogens while preserving protein structures and functions, and has the main advantage of not needing the addition of any photosensitizing additives (that might secondarily interfere with hMSCs). METHODOLOGY / PRINCIPAL FINDINGS: We applied the THERAFLEX UV-Platelets procedure on fresh platelet concentrates (PCs) suspended in platelet additive solution and prepared hPL from these treated PCs. We compared the quality and efficacy of PR-hPL with the corresponding non-PR ones. We found no impact on the content of five cytokines tested (EGF, bFGF, PDGF-AB, VEGF and IGF-1) but a significant decrease in TGF-ß1 (-21%, n = 11, p<0.01). We performed large-scale culture of hMSCs from bone marrow (BM) during three passages and showed that hPL or PR-hPL at 8% triggered comparable BM-hMSC proliferation as FBS at 10% plus bFGF. Moreover, after proliferation of hMSCs in an hPL- or PR-hPL-containing medium, their profile of membrane marker expression, their clonogenic potential and immunosuppressive properties were maintained, in comparison with BM-hMSCs cultured under FBS conditions. The potential to differentiate towards the adipogenic and osteogenic lineages of hMSCs cultured in parallel in the three conditions also remained identical. CONCLUSION / SIGNIFICANCE: We demonstrated the feasibility of using UV-C-treated platelets to subsequently obtain pathogen-reduced hPL, while preserving its optimal quality and efficacy for hMSC expansion in cell therapy applications.
format Online
Article
Text
id pubmed-5538655
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-55386552017-08-07 Pathogen reduction through additive-free short-wave UV light irradiation retains the optimal efficacy of human platelet lysate for the expansion of human bone marrow mesenchymal stem cells Viau, Sabrina Chabrand, Lucie Eap, Sandy Lorant, Judith Rouger, Karl Goudaliez, Francis Sumian, Chryslain Delorme, Bruno PLoS One Research Article BACKGROUND: We recently developed and characterized a standardized and clinical grade human Platelet Lysate (hPL) that constitutes an advantageous substitute for fetal bovine serum (FBS) for human mesenchymal stem cell (hMSC) expansion required in cell therapy procedures, avoiding xenogenic risks (virological and immunological) and ethical issues. Because of the progressive use of pathogen-reduced (PR) labile blood components, and the requirement of ensuring the viral safety of raw materials for cell therapy products, we evaluated the impact of the novel procedure known as THERAFLEX UV-Platelets for pathogen reduction on hPL quality (growth factors content) and efficacy (as a medium supplement for hMSC expansion). This technology is based on short-wave ultraviolet light (UV-C) that induces non-reversible damages in DNA and RNA of pathogens while preserving protein structures and functions, and has the main advantage of not needing the addition of any photosensitizing additives (that might secondarily interfere with hMSCs). METHODOLOGY / PRINCIPAL FINDINGS: We applied the THERAFLEX UV-Platelets procedure on fresh platelet concentrates (PCs) suspended in platelet additive solution and prepared hPL from these treated PCs. We compared the quality and efficacy of PR-hPL with the corresponding non-PR ones. We found no impact on the content of five cytokines tested (EGF, bFGF, PDGF-AB, VEGF and IGF-1) but a significant decrease in TGF-ß1 (-21%, n = 11, p<0.01). We performed large-scale culture of hMSCs from bone marrow (BM) during three passages and showed that hPL or PR-hPL at 8% triggered comparable BM-hMSC proliferation as FBS at 10% plus bFGF. Moreover, after proliferation of hMSCs in an hPL- or PR-hPL-containing medium, their profile of membrane marker expression, their clonogenic potential and immunosuppressive properties were maintained, in comparison with BM-hMSCs cultured under FBS conditions. The potential to differentiate towards the adipogenic and osteogenic lineages of hMSCs cultured in parallel in the three conditions also remained identical. CONCLUSION / SIGNIFICANCE: We demonstrated the feasibility of using UV-C-treated platelets to subsequently obtain pathogen-reduced hPL, while preserving its optimal quality and efficacy for hMSC expansion in cell therapy applications. Public Library of Science 2017-08-01 /pmc/articles/PMC5538655/ /pubmed/28763452 http://dx.doi.org/10.1371/journal.pone.0181406 Text en © 2017 Viau et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Viau, Sabrina
Chabrand, Lucie
Eap, Sandy
Lorant, Judith
Rouger, Karl
Goudaliez, Francis
Sumian, Chryslain
Delorme, Bruno
Pathogen reduction through additive-free short-wave UV light irradiation retains the optimal efficacy of human platelet lysate for the expansion of human bone marrow mesenchymal stem cells
title Pathogen reduction through additive-free short-wave UV light irradiation retains the optimal efficacy of human platelet lysate for the expansion of human bone marrow mesenchymal stem cells
title_full Pathogen reduction through additive-free short-wave UV light irradiation retains the optimal efficacy of human platelet lysate for the expansion of human bone marrow mesenchymal stem cells
title_fullStr Pathogen reduction through additive-free short-wave UV light irradiation retains the optimal efficacy of human platelet lysate for the expansion of human bone marrow mesenchymal stem cells
title_full_unstemmed Pathogen reduction through additive-free short-wave UV light irradiation retains the optimal efficacy of human platelet lysate for the expansion of human bone marrow mesenchymal stem cells
title_short Pathogen reduction through additive-free short-wave UV light irradiation retains the optimal efficacy of human platelet lysate for the expansion of human bone marrow mesenchymal stem cells
title_sort pathogen reduction through additive-free short-wave uv light irradiation retains the optimal efficacy of human platelet lysate for the expansion of human bone marrow mesenchymal stem cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538655/
https://www.ncbi.nlm.nih.gov/pubmed/28763452
http://dx.doi.org/10.1371/journal.pone.0181406
work_keys_str_mv AT viausabrina pathogenreductionthroughadditivefreeshortwaveuvlightirradiationretainstheoptimalefficacyofhumanplateletlysatefortheexpansionofhumanbonemarrowmesenchymalstemcells
AT chabrandlucie pathogenreductionthroughadditivefreeshortwaveuvlightirradiationretainstheoptimalefficacyofhumanplateletlysatefortheexpansionofhumanbonemarrowmesenchymalstemcells
AT eapsandy pathogenreductionthroughadditivefreeshortwaveuvlightirradiationretainstheoptimalefficacyofhumanplateletlysatefortheexpansionofhumanbonemarrowmesenchymalstemcells
AT lorantjudith pathogenreductionthroughadditivefreeshortwaveuvlightirradiationretainstheoptimalefficacyofhumanplateletlysatefortheexpansionofhumanbonemarrowmesenchymalstemcells
AT rougerkarl pathogenreductionthroughadditivefreeshortwaveuvlightirradiationretainstheoptimalefficacyofhumanplateletlysatefortheexpansionofhumanbonemarrowmesenchymalstemcells
AT goudaliezfrancis pathogenreductionthroughadditivefreeshortwaveuvlightirradiationretainstheoptimalefficacyofhumanplateletlysatefortheexpansionofhumanbonemarrowmesenchymalstemcells
AT sumianchryslain pathogenreductionthroughadditivefreeshortwaveuvlightirradiationretainstheoptimalefficacyofhumanplateletlysatefortheexpansionofhumanbonemarrowmesenchymalstemcells
AT delormebruno pathogenreductionthroughadditivefreeshortwaveuvlightirradiationretainstheoptimalefficacyofhumanplateletlysatefortheexpansionofhumanbonemarrowmesenchymalstemcells