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HPLs being prepared from pooled platelet concentrates, thereby increasing viral risks, manufacturing processes should incorporate robust virus\u2010reduction treatments. We evaluated a 19\u2009\u00b1\u20092\u2010nm virus removal nanofiltration process using hydrophilic regenerated cellulose hollow fibers on the properties of a neuroprotective heat\u2010treated HPL (HPPL). Spiking experiments demonstrated &gt;5.30 log removal of 20\u201322\u2010nm non\u2010enveloped minute virus of mice\u2010mock particles using an immuno\u2010quantitative polymerase chain reaction assay. The nanofiltered HPPL (NHPPL) contained a range of neurotrophic factors like HPPL. There was &gt;2 log removal of extracellular vesicles (EVs), associated with decreased expression of pro\u2010thrombogenic phosphatidylserine and procoagulant activity. LC\u2010MS\/MS proteomics showed that ca. 80% of HPPL proteins, including neurotrophins, cytokines, and antioxidants, were still found in NHPPL, whereas proteins associated with some infections and cancer\u2010associated pathways, pro\u2010coagulation and EVs, were removed. NHPPL maintained intact neuroprotective activity in Lund human mesencephalic dopaminergic neuron model of Parkinson's disease (PD), stimulated the differentiation of SH\u2010SY5Y neuronal cells and showed preserved anti\u2010inflammatory function upon intranasal administration in a mouse model of traumatic brain injury (TBI). Therefore, nanofiltration of HPL is feasible, lowers the viral, prothrombotic and procoagulant risks, and preserves the neuroprotective and anti\u2010inflammatory properties in neuronal pre\u2010clinical models of PD and TBI.<\/jats:p>","DOI":"10.1002\/btm2.10360","type":"journal-article","created":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T04:40:14Z","timestamp":1655786414000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Neuroprotective activity of a virus\u2010safe nanofiltered human platelet lysate depleted of extracellular vesicles in Parkinson's disease and traumatic brain injury models"],"prefix":"10.1002","volume":"8","author":[{"given":"Liling","family":"Delila","sequence":"first","affiliation":[{"name":"Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ouada","family":"Nebie","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering Taipei Medical University  Taipei Taiwan"},{"name":"Univ. 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