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

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 issue. Because of the progressive use of pathogen reduced (PR) labile blood components, we evaluated the impact of the novel procedure 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) and has the main advantage not to need the addition of any photosensitizing additive compounds (that might secondary interfere with hMSCs). We applied 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 showed no impact on the content in 5 cytokines tested (EGF, bFGF, PDGF-AB, VEGF and IGF-1) and a significant decrease in TGF-b1 (−21%, n = 16, p < 0.01). We performed large scale culture of hMSCs during 3 passages and showed that hPL or PR-hPL at 8% triggered comparable hMSC proliferation than FBS at 10% plus bFGF (n = 3). Moreover, after proliferation of hMSCs in hPL or PR-hPL containing medium, their profile of membrane marker expression, their clonogenic potential and immunosuppressive properties (inhibition of T-cell proliferation) were maintained, in comparison with hMSCs cultured in FBS conditions. We quantitatively compared the potential to differentiate in adipogenic and osteogenic lineages of hMSCs cultured in parallel in the 3 conditions and showed that they remained also identical. In conclusion, we demonstrated the feasibility to use UV-C treatment to subsequently obtain pathogen reduced hPL, while preserving its optimal quality and efficacy for hMSC expansion for cell therapy applications.