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Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Research Article

The Impact of Amotosalen Photochemical Pathogen Inactivation on Human Platelet Lysate

Author(s): Willem Delabie, Dominique De Bleser, Vicky Vandewalle, Marie-Laurence De Prest, Philippe Vandekerckhove, Veerle Compernolle and Hendrik B. Feys*

Volume 20, Issue 2, 2025

Published on: 20 June, 2024

Page: [218 - 227] Pages: 10

DOI: 10.2174/011574888X307274240610113314

Price: $65

Abstract

Background: Human Platelet Lysate (hPL) is a platelet-derived and growth factor-rich supplement for cell culture. It can be prepared from surplus platelet concentrates initially intended for transfusion. Amotosalen-based photochemical pathogen inactivation of platelet concentrates is used in a number of blood establishments worldwide to minimize the risk of pathogen transmission from donor to patient.

Methods: This pathogen inactivation method has not been formally validated for direct use on hPL. Here, we have studied the impact of pathogen inactivation on hPL and compared it to untreated hPL prepared from pathogen-inactivated platelet concentrates or control hPL. We used mass spectrometry, ELISA, and in vitro mesenchymal stem cell culture for determining residual amotosalen, final growth factor content, and cell doubling, respectively.

Results: The data have shown amotosalen concentrations to be reduced a thousand-fold following pathogen inactivation, leaving trace quantities of photosensitizer molecules in the final hPL product. Some growth factors have been reported to be significantly more impacted in hPL that is directly pathogen-inactivated compared to both control conditions. This has no significant effect on the growth kinetics of adipose-derived mesenchymal stem cells.

Conclusion: Direct amotosalen-based pathogen inactivation has a measurable impact on certain growth factors in hPL, but this does not outweigh the likely benefits of reducing the odds of donor-to-patient pathogen transmission.

Keywords: Human platelet lysate, pathogen inactivation, mesenchymal stem cells, amotosalen, mass spectrometry, stem cells.

« Previous
[1]
Doucet, C.; Ernou, I.; Zhang, Y.; Llense, J.R.; Begot, L.; Holy, X.; Lataillade, J.J. Platelet lysates promote mesenchymal stem cell expansion: A safety substitute for animal serum in cell-based therapy applications. J. Cell. Physiol., 2005, 205(2), 228-236.
[http://dx.doi.org/10.1002/jcp.20391] [PMID: 15887229]
[2]
Schallmoser, K.; Bartmann, C.; Rohde, E.; Reinisch, A.; Kashofer, K.; Stadelmeyer, E.; Drexler, C.; Lanzer, G.; Linkesch, W.; Strunk, D. Human platelet lysate can replace fetal bovine serum for clinical-scale expansion of functional mesenchymal stromal cells. Transfusion, 2007, 47(8), 1436-1446.
[http://dx.doi.org/10.1111/j.1537-2995.2007.01220.x] [PMID: 17655588]
[3]
Burnouf, T.; Strunk, D.; Koh, M.B.C.; Schallmoser, K. Human platelet lysate: Replacing fetal bovine serum as a gold standard for human cell propagation? Biomaterials, 2016, 76, 371-387.
[http://dx.doi.org/10.1016/j.biomaterials.2015.10.065] [PMID: 26561934]
[4]
Henschler, R.; Gabriel, C.; Schallmoser, K.; Burnouf, T.; Koh, M.B.C. Human platelet lysate current standards and future developments. Transfusion, 2019, 59(4), 1407-1413.
[http://dx.doi.org/10.1111/trf.15174] [PMID: 30741431]
[5]
Oeller, M.; Laner-Plamberger, S.; Krisch, L.; Rohde, E.; Strunk, D.; Schallmoser, K. Human platelet lysate for good manufacturing practice-compliant cell production. Int. J. Mol. Sci., 2021, 22(10), 5178.
[http://dx.doi.org/10.3390/ijms22105178] [PMID: 34068404]
[6]
Blümel, J.; Schwantes, A.; Baylis, S.A.; Stühler, A. Strategies toward virus and prion safe human platelet lysates. Transfusion, 2020, 60(1), 219-220.
[http://dx.doi.org/10.1111/trf.15581] [PMID: 31898348]
[7]
Brodersen, T.; Rostgaard, K.; Lau, C.J.; Juel, K.; Erikstrup, C.; Nielsen, K.R.; Ostrowski, S.R.; Titlestad, K.; Sækmose, S.G.; Pedersen, O.B.V.; Hjalgrim, H. The healthy donor effect and survey participation, becoming a donor and donor career. Transfusion, 2023, 63(1), 143-155.
[http://dx.doi.org/10.1111/trf.17190] [PMID: 36479702]
[8]
Feys, H.B.; Van Aelst, B.; Compernolle, V. Biomolecular consequences of platelet pathogen inactivation methods. Transfus. Med. Rev., 2019, 33(1), 29-34.
[http://dx.doi.org/10.1016/j.tmrv.2018.06.002] [PMID: 30021699]
[9]
Delabie, W.; De Bleser, D.; Vandewalle, V.; Vandekerckhove, P.; Compernolle, V.; Feys, H.B. Single step method for high yield human platelet lysate production. Transfusion, 2023, 63(2), 373-383.
[http://dx.doi.org/10.1111/trf.17188] [PMID: 36426732]
[10]
Hardwick, J. Blood processing. ISBT Sci. Ser., 2008, 3(2), 148-176.
[http://dx.doi.org/10.1111/j.1751-2824.2008.00195.x]
[11]
Van Aelst, B.; Feys, H.B.; Devloo, R.; Vanhoorelbeke, K.; Vandekerckhove, P.; Compernolle, V. Riboflavin and amotosalen photochemical treatments of platelet concentrates reduce thrombus formation kinetics in vitro. Vox Sang., 2015, 108(4), 328-339.
[http://dx.doi.org/10.1111/vox.12231] [PMID: 25557250]
[12]
Van Aelst, B.; Devloo, R.; Zachée, P.; t’Kindt, R.; Sandra, K.; Vandekerckhove, P.; Compernolle, V.; Feys, H.B. Psoralen and ultraviolet a light treatment directly affects phosphatidylinositol 3-kinase signal transduction by altering plasma membrane packing. J. Biol. Chem., 2016, 291(47), 24364-24376.
[http://dx.doi.org/10.1074/jbc.M116.735126] [PMID: 27687726]
[13]
Matthyssen, S.; Ní Dhubhghaill, S.; Van Gerwen, V.; Zakaria, N. Xeno-free cultivation of mesenchymal stem cells from the corneal stroma. Invest. Ophthalmol. Vis. Sci., 2017, 58(5), 2659-2665.
[http://dx.doi.org/10.1167/iovs.17-21676] [PMID: 28524929]
[14]
Janetzko, K.; Lin, L.; Eichler, H.; Mayaudon, V.; Flament, J.; Klüter, H. Implementation of the intercept blood system for platelets into routine blood bank manufacturing procedures: Evaluation of apheresis platelets. Vox Sang., 2004, 86(4), 239-245.
[http://dx.doi.org/10.1111/j.0042-9007.2004.00419.x] [PMID: 15144528]
[15]
Fernandez-Rebollo, E.; Mentrup, B.; Ebert, R.; Franzen, J.; Abagnale, G.; Sieben, T.; Ostrowska, A.; Hoffmann, P.; Roux, P.F.; Rath, B.; Goodhardt, M.; Lemaitre, J.M.; Bischof, O.; Jakob, F.; Wagner, W. Human platelet lysate versus fetal calf serum: These supplements do not select for different mesenchymal stromal cells. Sci. Rep., 2017, 7(1), 5132.
[http://dx.doi.org/10.1038/s41598-017-05207-1] [PMID: 28698620]
[16]
Hara, Y.; Steiner, M.; Baldini, M.G. Platelets as a source of growth-promoting factor(s) for tumor cells. Cancer Res., 1980, 40(4), 1212-1216.
[PMID: 7357550]
[17]
Bieback, K.A.R.E.N.; Fernandez-Muñoz, B.; Pati, S.; Schäfer, R. Gaps in the knowledge of human platelet lysate as a cell culture supplement for cell therapy: A joint publication from the AABB and the International Society for Cell & Gene Therapy. Cytotherapy, 2019, 21(9), 911-924.
[http://dx.doi.org/10.1016/j.jcyt.2019.06.006] [PMID: 31307904]
[18]
Stühler, A.; Blümel, J. Spezifische aspekte zur virussicherheit von produktionshilfsstoffen für somatische zelltherapie-arzneimittel. Federal Health Gazette Health Res. Health Protect, 2015, 58(11-12), 1233-1238.
[http://dx.doi.org/10.1007/s00103-015-2238-y] [PMID: 26383536]
[19]
Viau, S.; Eap, S.; Chabrand, L.; Lagrange, A.; Delorme, B. Viral inactivation of human platelet lysate by gamma irradiation preserves its optimal efficiency in the expansion of human bone marrow mesenchymal stromal cells. Transfusion, 2019, 59(3), 1069-1079.
[http://dx.doi.org/10.1111/trf.15205] [PMID: 30793328]
[20]
Lee, Y.L.; Lee, L.W.; Su, C.Y.; Hsiao, G.; Yang, Y.Y.; Leu, S.J.; Shieh, Y.H.; Burnouf, T. Virally inactivated human platelet concentrate lysate induces regulatory T cells and immunosuppressive effect in a murine asthma model. Transfusion, 2013, 53(9), 1918-1928.
[http://dx.doi.org/10.1111/trf.12068] [PMID: 23305248]
[21]
Wollowitz, S. Targeting DNA and RNA in pathogens: Mode of action of amotosalen HCl. Transfus. Med. Hemother., 2004, 31(1), 11-16.
[http://dx.doi.org/10.1159/000076975]
[22]
CFR. Code of Federal Regulations, general biological products standards, constituent materials. 2002. Available From: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=610&showFR=1
[23]
Castiglia, S.; Mareschi, K.; Labanca, L.; Lucania, G.; Leone, M.; Sanavio, F.; Castello, L.; Rustichelli, D.; Signorino, E.; Gunetti, M.; Bergallo, M.; Bordiga, A.M.; Ferrero, I.; Fagioli, F. Inactivated human platelet lysate with psoralen: A new perspective for mesenchymal stromal cell production in Good Manufacturing Practice conditions. Cytotherapy, 2014, 16(6), 750-763.
[http://dx.doi.org/10.1016/j.jcyt.2013.12.008] [PMID: 24529555]
[24]
Jonsdottir-Buch, S.M.; Sigurgrimsdottir, H.; Lieder, R.; Sigurjonsson, O.E. Expired and pathogen-inactivated platelet concentrates support differentiation and immunomodulation of mesenchymal stromal cells in culture. Cell Transplant., 2015, 24(8), 1545-1554.
[http://dx.doi.org/10.3727/096368914X683043] [PMID: 25198449]
[25]
Iudicone, P.; Fioravanti, D.; Bonanno, G.; Miceli, M.; Lavorino, C.; Totta, P.; Frati, L.; Nuti, M.; Pierelli, L. Pathogen-free, plasma-poor platelet lysate and expansion of human mesenchymal stem cells. J. Transl. Med., 2014, 12(1), 28.
[http://dx.doi.org/10.1186/1479-5876-12-28] [PMID: 24467837]
[26]
Nebie, O.; Devos, D.; Vingtdeux, V.; Barro, L.; Devedjian, J.C.; Jonneaux, A.; Chou, M.L.; Bordet, R.; Buée, L.; Knutson, F.; Blum, D.; Burnouf, T. The neuroprotective activity of heat-treated human platelet lysate biomaterials manufactured from outdated pathogen-reduced (amotosalen/UVA) platelet concentrates. J. Biomed. Sci., 2019, 26(1), 89.
[http://dx.doi.org/10.1186/s12929-019-0579-9] [PMID: 31666073]
[27]
Christensen, C.; Jonsdottir-Buch, S.M.; Sigurjonsson, O.E. Effects of amotosalen treatment on human platelet lysate bioactivity: A proof-of-concept study. PLoS One, 2020, 15(4), e0220163.
[http://dx.doi.org/10.1371/journal.pone.0220163] [PMID: 32294080]
[28]
Shanbhag, S.; Mohamed-Ahmed, S.; Lunde, T.H.F.; Suliman, S.; Bolstad, A.I.; Hervig, T.; Mustafa, K. Influence of platelet storage time on human platelet lysates and platelet lysate- expanded mesenchymal stromal cells for bone tissue engineering. Stem Cell Res. Ther., 2020, 11(1), 351.
[http://dx.doi.org/10.1186/s13287-020-01863-9] [PMID: 32962723]

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