Human nasal olfactory stem cells, purified as advanced therapy medicinal products, improve neuronal differentiation.
advanced therapy medicinal product
ecto-mesenchymal stem cell
neuronal differentiation
olfactory mucosa
olfactory stem cells as advanced therapy medicine
platelet lysate
regeneration
Journal
Frontiers in neuroscience
ISSN: 1662-4548
Titre abrégé: Front Neurosci
Pays: Switzerland
ID NLM: 101478481
Informations de publication
Date de publication:
2022
2022
Historique:
received:
12
09
2022
accepted:
04
11
2022
entrez:
5
12
2022
pubmed:
6
12
2022
medline:
6
12
2022
Statut:
epublish
Résumé
Olfactory ecto-mesenchymal stem cells (OE-MSC) are mesenchymal stem cells derived from the Nasal olfactory mucosa biopsies from three donors were used to design and validate the good manufacturing process for purifying stem cells. All processes and procedures were performed by expert staff from the cell therapy laboratory of the public hospital of Marseille (AP-HM), according to aseptic handling manipulations. Premises, materials and air were kept clean at all times to avoid cross-contamination, accidents, or even fatalities. Purified stem cells were cultivated for 24 or 48 h and conditioned media were collected before being added to the culture medium of the neuroblastoma cell line Neuro2a. Compared to the explant culture-based protocol, enzymatic digestion provides higher cell numbers more rapidly and is less prone to contamination. The use of platelet lysate in place of fetal calf serum is effective in promoting higher cell proliferation (the percentage of CFU-F progenitors is 15.5%), with the optimal percentage of platelet lysate being 10%. Cultured OE-MSCs do not show chromosomal rearrangement and, as expected, express the usual phenotypic markers of mesenchymal stem cells. When incorporated in standard culture medium, the conditioned medium of purified OE-MSCs promotes cell differentiation of Neuro2a neuroblastoma cells. We developed a safer and more efficient manufacturing process for clinical grade olfactory stem cells. With this protocol, human OE-MSCs will soon be used in a Phase I clinical based on their autologous transplantation in digital nerves with a neglected injury. However, further studies are required to unveil the underlying mechanisms of action.
Sections du résumé
Background
UNASSIGNED
Olfactory ecto-mesenchymal stem cells (OE-MSC) are mesenchymal stem cells derived from the
Methods
UNASSIGNED
Nasal olfactory mucosa biopsies from three donors were used to design and validate the good manufacturing process for purifying stem cells. All processes and procedures were performed by expert staff from the cell therapy laboratory of the public hospital of Marseille (AP-HM), according to aseptic handling manipulations. Premises, materials and air were kept clean at all times to avoid cross-contamination, accidents, or even fatalities. Purified stem cells were cultivated for 24 or 48 h and conditioned media were collected before being added to the culture medium of the neuroblastoma cell line Neuro2a.
Results
UNASSIGNED
Compared to the explant culture-based protocol, enzymatic digestion provides higher cell numbers more rapidly and is less prone to contamination. The use of platelet lysate in place of fetal calf serum is effective in promoting higher cell proliferation (the percentage of CFU-F progenitors is 15.5%), with the optimal percentage of platelet lysate being 10%. Cultured OE-MSCs do not show chromosomal rearrangement and, as expected, express the usual phenotypic markers of mesenchymal stem cells. When incorporated in standard culture medium, the conditioned medium of purified OE-MSCs promotes cell differentiation of Neuro2a neuroblastoma cells.
Conclusion
UNASSIGNED
We developed a safer and more efficient manufacturing process for clinical grade olfactory stem cells. With this protocol, human OE-MSCs will soon be used in a Phase I clinical based on their autologous transplantation in digital nerves with a neglected injury. However, further studies are required to unveil the underlying mechanisms of action.
Identifiants
pubmed: 36466172
doi: 10.3389/fnins.2022.1042276
pmc: PMC9713000
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1042276Informations de copyright
Copyright © 2022 Jaloux, Bonnet, Vogtensperger, Witters, Veran, Giraudo, Sabatier, Michel, Legré, Guiraudie-Capraz and Féron.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Int J Mol Sci. 2020 Apr 11;21(8):
pubmed: 32290426
Cells. 2019 Oct 08;8(10):
pubmed: 31597348
Stem Cells Dev. 2013 Nov 15;22(22):2990-3002
pubmed: 23819720
AAPS J. 2017 Nov 27;20(1):1
pubmed: 29181730
Behav Brain Res. 2021 May 7;405:113205
pubmed: 33636233
Curr Stem Cell Res Ther. 2011 Jun;6(2):105-14
pubmed: 21190535
Cells Tissues Organs. 2020;209(4-6):257-265
pubmed: 33752213
J Vis Exp. 2011 Aug 22;(54):
pubmed: 21876529
J Comp Neurol. 1998 Nov 2;400(4):469-86
pubmed: 9786409
Stem Cells Int. 2017;2017:1478606
pubmed: 28698717
Transfusion. 2007 Aug;47(8):1436-46
pubmed: 17655588
J Transl Med. 2020 Sep 15;18(1):351
pubmed: 32933520
Mol Neurobiol. 2022 Dec;59(12):7323-7336
pubmed: 36173534
Stem Cells. 2008 Aug;26(8):2183-92
pubmed: 18535154
Stem Cell Rev Rep. 2012 Sep;8(3):658-71
pubmed: 22170630
J Transl Med. 2014 Jan 27;12:28
pubmed: 24467837
Biomaterials. 2016 Jan;76:371-87
pubmed: 26561934
Neurotox Res. 2021 Jun;39(3):598-608
pubmed: 33433781
J Neurotrauma. 2018 Aug 1;35(15):1765-1780
pubmed: 29357739
Transfusion. 2019 Mar;59(3):1069-1079
pubmed: 30793328
Stem Cells Dev. 2010 Jun;19(6):853-66
pubmed: 19905894
Transfus Med Hemother. 2013 Oct;40(5):326-35
pubmed: 24273486
J Chem Neuroanat. 2021 Jul;114:101961
pubmed: 33933574
Front Cell Neurosci. 2020 Nov 12;14:580206
pubmed: 33281557
Brain Res. 2001 Jan 26;890(1):11-22
pubmed: 11164764
Stem Cell Res Ther. 2019 Dec 21;10(1):406
pubmed: 31864423
Aging (Albany NY). 2021 Apr 4;13(8):11234-11256
pubmed: 33820869
Biomolecules. 2022 Jun 11;12(6):
pubmed: 35740943
Bull Exp Biol Med. 2020 Feb;168(4):538-541
pubmed: 32157509
Stem Cells Int. 2019 May 19;2019:2945435
pubmed: 31236114
Stem Cell Res Ther. 2018 May 2;9(1):124
pubmed: 29720245
Cells. 2019 Jul 15;8(7):
pubmed: 31311198
Biologicals. 2013 Nov;41(6):407-14
pubmed: 24071554
Cell Prolif. 2017 Apr;50(2):
pubmed: 28144997
Mol Neurobiol. 2018 Oct;55(10):8014-8037
pubmed: 29498005
Regen Med. 2018 Jul 1;13(5):581-593
pubmed: 30113240
Ann Med. 2005;37(7):469-79
pubmed: 16278160
J Chem Neuroanat. 2022 Mar;120:102071
pubmed: 35051594
J Hematol Oncol. 2021 Feb 12;14(1):24
pubmed: 33579329
J Chem Neuroanat. 2021 Mar;112:101903
pubmed: 33278568
Glia. 2010 Jan 15;58(2):125-34
pubmed: 19606497
Dev Dyn. 2005 Jun;233(2):496-515
pubmed: 15782416
J Clin Invest. 2011 Jul;121(7):2808-20
pubmed: 21670501
Acta Neuropathol Commun. 2022 Jan 29;10(1):12
pubmed: 35093166
J Cell Physiol. 2005 Nov;205(2):228-36
pubmed: 15887229
Stem Cells. 2011 Apr;29(4):670-7
pubmed: 21312317
Clin Rev Allergy Immunol. 2017 Apr;52(2):234-259
pubmed: 27207172
Plast Reconstr Surg. 2020 Dec;146(6):1295-1305
pubmed: 33234960
Int J Mol Sci. 2021 May 13;22(10):
pubmed: 34068404
Head Neck. 2016 Apr;38 Suppl 1:E2011-20
pubmed: 26829770
J Neurocytol. 1979 Apr;8(2):197-213
pubmed: 469573
Glia. 2017 Apr;65(4):639-656
pubmed: 28144983
Proc Natl Acad Sci U S A. 2009 Jun 2;106(22):8947-52
pubmed: 19447928
J Clin Cell Immunol. 2013 Jun 1;4(3):
pubmed: 24244890
N Engl J Med. 1957 Sep 12;257(11):491-6
pubmed: 13464965
Dis Model Mech. 2010 Nov-Dec;3(11-12):785-98
pubmed: 20699480