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Retinal ganglion cells were counted in isolated retinas, and optic nerves were assessed for inflammation and demyelination. ST266 treatment significantly improved retinal ganglion cell survival and reduced optic nerve demyelination in EAE mice. The lower molecular weight ST266 fraction significantly improved optic nerve demyelination, but only showed a trend towards improved retinal ganglion cell survival. ST266 fractions below 50kDa increased Schwann cell proliferation in vitro, but were less effective than non-fractionated ST266. Demyelination attenuation was partially associated with the lower molecular weight ST266 fraction, but removal of higher molecular weight biomolecules from ST266 diminishes its neuroprotective effects, suggesting at least some high molecular weight proteins play a role in ST266-mediated neuroprotection.<\/jats:p>","DOI":"10.1371\/journal.pone.0243862","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T18:39:18Z","timestamp":1609958358000},"page":"e0243862","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Neuroprotection mediated by ST266 requires full complement of proteins secreted by amnion-derived multipotent progenitor cells"],"prefix":"10.1371","volume":"16","author":[{"given":"Keirnan","family":"Willett","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reas S.","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5569-7261","authenticated-orcid":true,"given":"Kimberly","family":"Dine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard","family":"Wessel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6570-4602","authenticated-orcid":true,"given":"Ziv Z.","family":"Kirshner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodie L.","family":"Sauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Ellis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry R.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2417-258X","authenticated-orcid":true,"given":"Kenneth S.","family":"Shindler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,1,6]]},"reference":[{"key":"pone.0243862.ref001","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.jocn.2017.06.005","article-title":"Multiple sclerosis: Frequency, cost, and economic burden in the United States","volume":"45","author":"AY Chen","year":"2017","journal-title":"J Clin Neurosci"},{"key":"pone.0243862.ref002","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1056\/NEJM199202273260901","article-title":"A Randomized, Controlled Trial of Corticosteroids in the Treatment of Acute Optic Neuritis","volume":"326","author":"RW Beck","year":"1992","journal-title":"N Engl J Med"},{"key":"pone.0243862.ref003","first-page":"155","article-title":"Effect of human amnion-derived multipotent progenitor cells on hematopoietic recovery after total body irradiation in C57BL \/ 6 mice","volume":"16","author":"Y Du","year":"2018","journal-title":"Int J Radiat Res"},{"key":"pone.0243862.ref004","doi-asserted-by":"crossref","first-page":"41768","DOI":"10.1038\/srep41768","article-title":"Intranasal Delivery of A Novel Amnion Cell Secretome Prevents Neuronal Damage and Preserves Function In A Mouse Multiple Sclerosis Model","volume":"7","author":"RS Khan","year":"2017","journal-title":"Sci Rep"},{"key":"pone.0243862.ref005","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1097\/WNO.0000000000000760","article-title":"Effects of Varying Intranasal Treatment Regimens in ST266-Mediated Retinal Ganglion Cell Neuroprotection","volume":"39","author":"RS Khan","year":"2019","journal-title":"J neuro-ophthalmology"},{"key":"pone.0243862.ref006","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.1167\/iovs.18-24096","article-title":"RGC neuroprotection following optic nerve trauma mediated by intranasal delivery of amnion cell secretome","volume":"59","author":"GA Grinblat","year":"2018","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"pone.0243862.ref007","first-page":"e18","article-title":"Amnion-derived cellular cytokine solution: a physiological combination of cytokines for wound healing","volume":"8","author":"DL Steed","year":"2008","journal-title":"Eplasty"},{"key":"pone.0243862.ref008","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/0003-2697(76)90251-7","article-title":"Hexokinase binding to polypropylene test tubes. 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