{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T00:33:31Z","timestamp":1794357211161,"version":"4.9.0"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T00:00:00Z","timestamp":1668643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007380","name":"Fondation de l'Avenir pour la Recherche M\u00e9dicale Appliqu\u00e9e","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007380","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Olfactory ecto-mesenchymal stem cells (OE-MSC) are mesenchymal stem cells derived from the <jats:italic>lamina propria<\/jats:italic> of the nasal mucosa. They display neurogenic and immunomodulatory properties and were shown to induce recovery in animal models of spinal cord trauma, hearing loss, Parkinsons\u2019s disease, amnesia, and peripheral nerve injury. As a step toward clinical practice, we sought to (i) devise a culture protocol that meets the requirements set by human health agencies and (ii) assess the efficacy of stem cells on neuron differentiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnins.2022.1042276","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T06:09:56Z","timestamp":1668665396000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Human nasal olfactory stem cells, purified as advanced therapy medicinal products, improve neuronal differentiation"],"prefix":"10.3389","volume":"16","author":[{"given":"Charlotte","family":"Jaloux","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxime","family":"Bonnet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Vogtensperger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Witters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Veran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Giraudo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Sabatier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Michel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regis","family":"Legr\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga\u00eblle","family":"Guiraudie-Capraz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"F\u00e9ron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12060818","article-title":"Effects of olfactory mucosa stem\/stromal cell and olfactory ensheating cells secretome on peripheral nerve regeneration.","volume":"12","author":"Alvites","year":"2022","journal-title":"Biomolecules"},{"key":"B2","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1159\/000513604","article-title":"Adipose-derived stromal\/stem cell culture: Effects of different concentrations of human platelet lysate in media.","volume":"209","author":"Ballesteros","year":"2020","journal-title":"Cells Tissues Organs."},{"key":"B3","doi-asserted-by":"publisher","first-page":"E2011","DOI":"10.1002\/hed.24371","article-title":"Human olfactory stem cells for injured facial nerve reconstruction in a rat model.","volume":"38","author":"Batioglu-Karaaltin","year":"2016","journal-title":"Head Neck"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchemneu.2020.101903","article-title":"Bilateral striatal transplantation of human olfactory stem cells ameliorates motor function, prevents necroptosis-induced cell death and improves striatal volume in the rat model of Huntington\u2019s disease.","volume":"112","author":"Bayat","year":"2021","journal-title":"J. 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