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...
Saved in:
| Published in | PloS one Vol. 16; no. 1; p. e0243862 |
|---|---|
| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Public Library of Science
06.01.2021
Public Library of Science (PLoS) |
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Summary: | 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. |
|---|---|
| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: The ST266 therapy studied here is proprietary property of Noveome Biotherapeutics, Inc. I, Kenneth Shindler, corresponding author for this manuscript, have previously received honoraria from and served on Scientific Advisory Boards from Noveome, and have received sponsored research funding from Noveome for other projects in the past, with no current funding. For the in vivo studies described in the current manuscript, Noveome provided ST266 to my lab at no cost, but funding for all other study materials and personnel was provided by grants from NIH and non-profit foundations. The manuscript does also include in vitro cell assay data from experiments performed by our collaborators at Noveome. Co-authors (HW, ZK, JS, AE, LB) from Noveome were involved in design and completion of the in vitro studies, but all in vivo studies on optic neuritis, which represent the majority of experiments in this manuscript, were designed and conducted without influence from any of the Noveome employees to reduce any potential conflicts of interest. Neither I, nor any of my lab members (coauthors KW, RK, KD), have any financial stake in Noveome or ST266. These competing interests do not alter our adherence to PLOS ONE policies on sharing data and materials. |
| ISSN: | 1932-6203 1932-6203 |
| DOI: | 10.1371/journal.pone.0243862 |