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

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


Title: Effects of amotosalen treatment on human platelet lysate bioactivity: A proof-of-concept study
Author: Christensen, Christian
Jonsdottir-Buch, Sandra Mjoll   orcid.org/0000-0002-1845-5420
Sigurjonsson, Olafur   orcid.org/0000-0002-4968-842X
Date: 2020-04-15
Language: English
Scope: e0220163
University/Institute: Háskóli Íslands
University of Iceland
Háskólinn í Reykjavík
Reykjavik University
School: Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Tæknisvið (HR)
School of Technology (RU)
Department: Læknadeild (HÍ)
Faculty of Medicine (UI)
Series: PLOS ONE;15(4)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0220163
Subject: Platelets; Cell differentiation; Cell cultures; Growth factors; Frumurannsóknir
URI: https://hdl.handle.net/20.500.11815/2389

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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

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.

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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.

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