Neuroprotection mediated by ST266 requires full complement of proteins secreted by amnion-derived multipotent progenitor cells
ST266 is the biological secretome of cultured Amnion-derived Multipotent Progenitor cells containing multiple growth factors and cytokines. While intranasally-administered ST266 improves the phenotype in experimental optic neuritis, specific ST266 components mediating these effects are not known. We...
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description | ST266 is the biological secretome of cultured Amnion-derived Multipotent Progenitor cells containing multiple growth factors and cytokines. While intranasally-administered ST266 improves the phenotype in experimental optic neuritis, specific ST266 components mediating these effects are not known. We compared the effects of ST266 with and without removal of large molecular weight proteins both in vitro and in the multiple sclerosis model experimental autoimmune encephalomyelitis (EAE) in C57BL/6J mice. Mice were treated daily with intranasal vehicle, ST266 or lower molecular weight fraction of ST266. 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. |
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While intranasally-administered ST266 improves the phenotype in experimental optic neuritis, specific ST266 components mediating these effects are not known. We compared the effects of ST266 with and without removal of large molecular weight proteins both in vitro and in the multiple sclerosis model experimental autoimmune encephalomyelitis (EAE) in C57BL/6J mice. Mice were treated daily with intranasal vehicle, ST266 or lower molecular weight fraction of ST266. 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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0243862</identifier><identifier>PMID: 33406093</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Amnion ; Amnion - cytology ; Animals ; Attenuation ; Biological products ; Biology and Life Sciences ; Biomolecules ; Care and treatment ; Cell growth ; Cell Proliferation ; Cell survival ; Cells (biology) ; Cellular proteins ; Complications and side effects ; Cytokines ; Demyelinating Diseases - complications ; Demyelinating Diseases - pathology ; Demyelination ; Encephalomyelitis ; Encephalomyelitis, Autoimmune, Experimental - complications ; Encephalomyelitis, Autoimmune, Experimental - pathology ; Experimental allergic encephalomyelitis ; Experiments ; Female ; Gait ; Genetic aspects ; Growth factors ; Health aspects ; Manufacturers ; Medicine and Health Sciences ; Mice ; Mice, Inbred C57BL ; Molecular Weight ; Multiple sclerosis ; Multipotent Stem Cells - cytology ; Myelin-Oligodendrocyte Glycoprotein ; Nerves ; Neuritis ; Neurologic manifestations of general diseases ; Neuroprotection ; Optic nerve ; Optic Nerve - pathology ; Optic neuritis ; Optic Neuritis - complications ; Optic Neuritis - pathology ; Peptides ; Phenotypes ; Prevention ; Progenitor cells ; Proteins ; Research and Analysis Methods ; Retina ; Retinal ganglion cells ; Retinal Ganglion Cells - pathology ; Schwann Cells - pathology ; Secretome ; Stem cells ; Survival ; Tuberculosis</subject><ispartof>PloS one, 2021-01, Vol.16 (1), p.e0243862-e0243862</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Willett et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 Willett et al 2021 Willett et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-32fdbc47cd06888e06460f1d2d1b7209e932897226f9eae17ed3bc34763bd3303</citedby><cites>FETCH-LOGICAL-c692t-32fdbc47cd06888e06460f1d2d1b7209e932897226f9eae17ed3bc34763bd3303</cites><orcidid>0000-0001-5569-7261 ; 0000-0002-6570-4602 ; 0000-0003-2417-258X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787369/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787369/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33406093$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Kihara, Alexandre Hiroaki</contributor><creatorcontrib>Willett, Keirnan</creatorcontrib><creatorcontrib>Khan, Reas S</creatorcontrib><creatorcontrib>Dine, Kimberly</creatorcontrib><creatorcontrib>Wessel, Howard</creatorcontrib><creatorcontrib>Kirshner, Ziv Z</creatorcontrib><creatorcontrib>Sauer, Jodie L</creatorcontrib><creatorcontrib>Ellis, Ashley</creatorcontrib><creatorcontrib>Brown, Larry R</creatorcontrib><creatorcontrib>Shindler, Kenneth S</creatorcontrib><title>Neuroprotection mediated by ST266 requires full complement of proteins secreted by amnion-derived multipotent progenitor cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>ST266 is the biological secretome of cultured Amnion-derived Multipotent Progenitor cells containing multiple growth factors and cytokines. While intranasally-administered ST266 improves the phenotype in experimental optic neuritis, specific ST266 components mediating these effects are not known. We compared the effects of ST266 with and without removal of large molecular weight proteins both in vitro and in the multiple sclerosis model experimental autoimmune encephalomyelitis (EAE) in C57BL/6J mice. Mice were treated daily with intranasal vehicle, ST266 or lower molecular weight fraction of ST266. 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. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Willett, Keirnan</au><au>Khan, Reas S</au><au>Dine, Kimberly</au><au>Wessel, Howard</au><au>Kirshner, Ziv Z</au><au>Sauer, Jodie L</au><au>Ellis, Ashley</au><au>Brown, Larry R</au><au>Shindler, Kenneth S</au><au>Kihara, Alexandre Hiroaki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neuroprotection mediated by ST266 requires full complement of proteins secreted by amnion-derived multipotent progenitor cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2021-01-06</date><risdate>2021</risdate><volume>16</volume><issue>1</issue><spage>e0243862</spage><epage>e0243862</epage><pages>e0243862-e0243862</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>ST266 is the biological secretome of cultured Amnion-derived Multipotent Progenitor cells containing multiple growth factors and cytokines. While intranasally-administered ST266 improves the phenotype in experimental optic neuritis, specific ST266 components mediating these effects are not known. We compared the effects of ST266 with and without removal of large molecular weight proteins both in vitro and in the multiple sclerosis model experimental autoimmune encephalomyelitis (EAE) in C57BL/6J mice. Mice were treated daily with intranasal vehicle, ST266 or lower molecular weight fraction of ST266. 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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33406093</pmid><doi>10.1371/journal.pone.0243862</doi><tpages>e0243862</tpages><orcidid>https://orcid.org/0000-0001-5569-7261</orcidid><orcidid>https://orcid.org/0000-0002-6570-4602</orcidid><orcidid>https://orcid.org/0000-0003-2417-258X</orcidid><oa>free_for_read</oa></addata></record> |
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recordid | cdi_plos_journals_2475829505 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Amnion Amnion - cytology Animals Attenuation Biological products Biology and Life Sciences Biomolecules Care and treatment Cell growth Cell Proliferation Cell survival Cells (biology) Cellular proteins Complications and side effects Cytokines Demyelinating Diseases - complications Demyelinating Diseases - pathology Demyelination Encephalomyelitis Encephalomyelitis, Autoimmune, Experimental - complications Encephalomyelitis, Autoimmune, Experimental - pathology Experimental allergic encephalomyelitis Experiments Female Gait Genetic aspects Growth factors Health aspects Manufacturers Medicine and Health Sciences Mice Mice, Inbred C57BL Molecular Weight Multiple sclerosis Multipotent Stem Cells - cytology Myelin-Oligodendrocyte Glycoprotein Nerves Neuritis Neurologic manifestations of general diseases Neuroprotection Optic nerve Optic Nerve - pathology Optic neuritis Optic Neuritis - complications Optic Neuritis - pathology Peptides Phenotypes Prevention Progenitor cells Proteins Research and Analysis Methods Retina Retinal ganglion cells Retinal Ganglion Cells - pathology Schwann Cells - pathology Secretome Stem cells Survival Tuberculosis |
title | Neuroprotection mediated by ST266 requires full complement of proteins secreted by amnion-derived multipotent progenitor cells |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-25T23%3A40%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Neuroprotection%20mediated%20by%20ST266%20requires%20full%20complement%20of%20proteins%20secreted%20by%20amnion-derived%20multipotent%20progenitor%20cells&rft.jtitle=PloS%20one&rft.au=Willett,%20Keirnan&rft.date=2021-01-06&rft.volume=16&rft.issue=1&rft.spage=e0243862&rft.epage=e0243862&rft.pages=e0243862-e0243862&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0243862&rft_dat=%3Cgale_plos_%3EA647638975%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2475829505&rft_id=info:pmid/33406093&rft_galeid=A647638975&rft_doaj_id=oai_doaj_org_article_ed87775114e3425c94711c78818923c0&rfr_iscdi=true |