Short-Term Rapamycin Preconditioning Diminishes Therapeutic Efficacy of Human Adipose-Derived Stem Cells in a Murine Model of Multiple Sclerosis

Simple item page
dc.creatorWise, Rachel M.
dc.creatorHarrison, Mark A. A.
dc.creatorSullivan, Brianne N.
dc.creatorAl-Ghadban, Sara
dc.creatorAleman, Sarah J.
dc.creatorVinluan, Amber T.
dc.creatorMonaco, Emily R.
dc.creatorDonato, Umberto M.
dc.creatorPursell, India A.
dc.creatorBunnell, Bruce A.
dc.creator.orcid0000-0001-6196-3722 (Bunnell, Bruce A.)
dc.date.accessioned2022-08-25T15:39:46Z
dc.date.available2022-08-25T15:39:46Z
dc.date.issued2020-09-30
dc.description.abstractHuman adipose-derived stem cells (ASCs) show immense promise for treating inflammatory diseases, attributed primarily to their potent paracrine signaling. Previous investigations demonstrated that short-term Rapamycin preconditioning of bone marrow-derived stem cells (BMSCs) elevated secretion of prostaglandin E2, a pleiotropic molecule with therapeutic effects in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS), and enhanced immunosuppressive capacity in vitro. However, this has yet to be examined in ASCs. The present study examined the therapeutic potential of short-term Rapamycin-preconditioned ASCs in the EAE model. Animals were treated at peak disease with control ASCs (EAE-ASCs), Rapa-preconditioned ASCs (EAE-Rapa-ASCs), or vehicle control (EAE). Results show that EAE-ASCs improved clinical disease scores and elevated intact myelin compared to both EAE and EAE-Rapa-ASC animals. These results correlated with augmented CD4⁺ T helper (Th) and T regulatory (Treg) cell populations in the spinal cord, and increased gene expression of interleukin-10 (IL-10), an anti-inflammatory cytokine. Conversely, EAE-Rapa-ASC mice showed no improvement in clinical disease scores, reduced myelin levels, and significantly less Th and Treg cells in the spinal cord. These findings suggest that short-term Rapamycin preconditioning reduces the therapeutic efficacy of ASCs when applied to late-stage EAE.
dc.description.sponsorshipThe funds used for these studies were private funds from Tulane University.
dc.identifier.citationWise, R. M., Harrison, M., Sullivan, B. N., Al-Ghadban, S., Aleman, S. J., Vinluan, A. T., Monaco, E. R., Donato, U. M., Pursell, I. A., & Bunnell, B. A. (2020). Short-Term Rapamycin Preconditioning Diminishes Therapeutic Efficacy of Human Adipose-Derived Stem Cells in a Murine Model of Multiple Sclerosis. Cells, 9(10), 2218. https://doi.org/10.3390/cells9102218
dc.identifier.issn2073-4409
dc.identifier.issue10
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31651
dc.identifier.volume9
dc.publisherMDPI
dc.relation.urihttps://doi.org/10.3390/cells9102218
dc.rights.holder© 2020 by the authors.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceCells
dc.subjectRapamycin
dc.subjectadipose tissue-derived stem cells (ASCs)
dc.subjectdemyelination
dc.subjectexperimental autoimmune encephalomyelitis (EAE)
dc.subjectimmunomodulation
dc.subjectinflammation
dc.subjectmultiple sclerosis (MS)
dc.subject.meshAnimals
dc.subject.meshAnti-Bacterial Agents / pharmacology
dc.subject.meshAnti-Bacterial Agents / therapeutic use
dc.subject.meshDisease Models, Animal
dc.subject.meshHumans
dc.subject.meshMesenchymal Stem Cell Transplantation / methods
dc.subject.meshMesenchymal Stem Cells / metabolism
dc.subject.meshMice
dc.subject.meshMultiple Sclerosis / drug therapy
dc.subject.meshSirolimus / adverse effects
dc.subject.meshSirolimus / pharmacology
dc.titleShort-Term Rapamycin Preconditioning Diminishes Therapeutic Efficacy of Human Adipose-Derived Stem Cells in a Murine Model of Multiple Sclerosis
dc.typeArticle
dc.type.materialtext

Files

Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
Name:
10.3390_cells9102218.pdf
Size:
1.53 MB
Format:
Adobe Portable Document Format
Description:
full text article
Download

Collections

Publications -- Bruce Bunnell