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Open AccessArticle

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

1
Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118, USA
2
Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA
3
Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USA
4
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA
*
Author to whom correspondence should be addressed.
Cells 2020, 9(10), 2218; https://doi.org/10.3390/cells9102218
Received: 24 August 2020 / Revised: 16 September 2020 / Accepted: 28 September 2020 / Published: 30 September 2020
(This article belongs to the Special Issue Human Adipose Stem Cells)
Human 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. View Full-Text
Keywords: adipose tissue-derived stem cells (ASCs); multiple sclerosis (MS); experimental autoimmune encephalomyelitis (EAE); Rapamycin; immunomodulation; inflammation; demyelination adipose tissue-derived stem cells (ASCs); multiple sclerosis (MS); experimental autoimmune encephalomyelitis (EAE); Rapamycin; immunomodulation; inflammation; demyelination
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MDPI and ACS Style

Wise, R.M.; Harrison, M.A.A.; Sullivan, B.N.; Al-Ghadban, S.; Aleman, S.J.; Vinluan, A.T.; Monaco, E.R.; Donato, U.M.; Pursell, I.A.; Bunnell, B.A. Short-Term Rapamycin Preconditioning Diminishes Therapeutic Efficacy of Human Adipose-Derived Stem Cells in a Murine Model of Multiple Sclerosis. Cells 2020, 9, 2218. https://doi.org/10.3390/cells9102218

AMA Style

Wise RM, Harrison MAA, Sullivan BN, Al-Ghadban S, Aleman SJ, Vinluan AT, Monaco ER, Donato UM, Pursell IA, Bunnell BA. Short-Term Rapamycin Preconditioning Diminishes Therapeutic Efficacy of Human Adipose-Derived Stem Cells in a Murine Model of Multiple Sclerosis. Cells. 2020; 9(10):2218. https://doi.org/10.3390/cells9102218

Chicago/Turabian Style

Wise, Rachel M.; Harrison, Mark A.A.; Sullivan, Brianne N.; Al-Ghadban, Sara; Aleman, Sarah J.; Vinluan, Amber T.; Monaco, Emily R.; Donato, Umberto M.; Pursell, India A.; Bunnell, Bruce A. 2020. "Short-Term Rapamycin Preconditioning Diminishes Therapeutic Efficacy of Human Adipose-Derived Stem Cells in a Murine Model of Multiple Sclerosis" Cells 9, no. 10: 2218. https://doi.org/10.3390/cells9102218

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