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

• Published in: Cells (Basel, Switzerland) Switzerland), 2020-09, Vol.9 (10), p.2218
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: adipose tissue-derived stem cells (ASCs); Animal models; Animals; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Bone marrow; Care and treatment; CD4 antigen; Cytokines; Disease; Disease Models, Animal; Experimental allergic encephalomyelitis; experimental autoimmune encephalomyelitis (EAE); Gene expression; Health aspects; Humans; immunomodulation; Inflammation; Inflammatory diseases; Interleukin 10; Laboratories; Lymphocytes T; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stem Cells - metabolism; Mice; Multiple sclerosis; multiple sclerosis (MS); Multiple Sclerosis - drug therapy; Myelin; Paracrine signalling; Patient outcomes; Peptides; Prostaglandin E2; Quorum sensing; Rapamycin; Sirolimus - adverse effects; Sirolimus - pharmacology; Spinal cord; Stem cell transplantation; Stem cells; Transplantation; Whooping cough
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells9102218

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 (T ) and T regulatory (T ) 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 T and T 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.