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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Veröffentlicht in:PloS one 2021-01, Vol.16 (1), p.e0243862-e0243862
Hauptverfasser: Willett, Keirnan, Khan, Reas S, Dine, Kimberly, Wessel, Howard, Kirshner, Ziv Z, Sauer, Jodie L, Ellis, Ashley, Brown, Larry R, Shindler, Kenneth S
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creator Willett, Keirnan
Khan, Reas S
Dine, Kimberly
Wessel, Howard
Kirshner, Ziv Z
Sauer, Jodie L
Ellis, Ashley
Brown, Larry R
Shindler, Kenneth S
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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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. 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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
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