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The neuroprotective activity of heat-treated human platelet lysate biomaterials manufactured from outdated pathogen-reduced (amotosalen/UVA) platelet concentrates
Taipei Med Univ, Coll Biomed Engn, Grad Inst Biomed Mat & Tissue Engn, 250 Wu Xing St, Taipei 11031, Taiwan.ORCID iD: 0000-0002-6802-4215
Univ Lille, Inserm, F-59000 Lille, France.ORCID iD: 0000-0002-2417-799X
CHU Lille, Lille Neurosci & Cognit Degenerat & Vasc Cogn Dis, UMRS1171, F-59000 Lille, France.ORCID iD: 0000-0003-4550-503X
Taipei Med Univ, Coll Biomed Engn, Int PhD Program Biomed Engn, Taipei, Taiwan.ORCID iD: 0000-0002-2202-9731
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2019 (English)In: Journal of Biomedical Science, ISSN 1021-7770, E-ISSN 1423-0127, Vol. 26, article id 89Article in journal (Refereed) Published
Abstract [en]

Background: Effective neurorestorative therapies of neurodegenerative diseases must be developed. There is increasing interest in using human platelet lysates, rich in neurotrophic factors, as novel disease-modifying strategy of neurodegeneration. To ensure virus safety, pathogen reduction treatments should be incorporated in the preparation process of the platelet concentrates used as source material. We therefore investigated whether platelet concentrates (PC) pathogen-inactivated using a licensed photo-inactivation treatment combining photosensitive psoralen (amotosalen) and UVA irradiation (Intercept) can serve as source material to prepare platelet lysates with preserved neuroprotective activity in Parkinson's disease models.

Methods: Intercept treated-PCs were centrifuged, when reaching expiry day (7 days after collection), to remove plasma and platelet additive solution. The platelet pellet was re-suspended and concentrated in phosphate buffer saline, subjected to 3 freeze-thaw cycles (-80 degrees C/37 degrees C) then centrifuged to remove cell debris. The supernatant was recovered and further purified, or not, by heat-treatment as in our previous investigations. The content in proteins and neurotrophic factors was determined and the toxicity and neuroprotective activity of the platelet lysates towards LUHMES cells or primary cortical/hippocampal neurons were assessed using ELISA, flow cytometry, cell viability and cytotoxicity assays and proteins analysis by Western blot.

Results: Platelet lysates contained the expected level of total proteins (ca. 7-14 mg/mL) and neurotrophic factors. Virally inactivated and heat-treated platelet lysates did not exert detectable toxic effects on neither Lund human mesencephalic dopaminergic LUHMES cell line nor primary neurons. When used at doses of 5 and 0.5%, they enhanced the expression of tyrosine hydroxylase and neuron-specific enolase in LUHMES cells and did not significantly impact synaptic protein expression in primary neurons, respectively. Furthermore, virally-inactivated platelet lysates tested were found to exert very strong neuroprotection effects on both LUHMES and primary neurons exposed to erastin, an inducer of ferroptosis cell death.

Conclusion: Outdated Intercept pathogen-reduced platelet concentrates can be used to prepare safe and highly neuroprotective human heat-treated platelet pellet lysates. These data open reassuring perspectives in the possibility to develop an effective biotherapy using virally-inactivated platelet lysates rich in functional neurotrophins for neuroregenerative medicine, and for further bio-industrial development. However, the data should be confirmed in animal models.

Place, publisher, year, edition, pages
BMC , 2019. Vol. 26, article id 89
Keywords [en]
Pathogen inactivation, Intercept-platelet lysate, Ferroptosis, Neuroprotection, LUHMES cells, Primary neurons, Synaptic markers
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:uu:diva-402852DOI: 10.1186/s12929-019-0579-9ISI: 000505707400001PubMedID: 31666073OAI: oai:DiVA.org:uu-402852DiVA, id: diva2:1387526
Available from: 2020-01-22 Created: 2020-01-22 Last updated: 2020-01-22Bibliographically approved

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