Short-Term Rapamycin Preconditioning Diminishes Therapeutic Efficacy of Human Adipose-Derived Stem Cells in a Murine Model of Multiple Sclerosis
| العنوان: | Short-Term Rapamycin Preconditioning Diminishes Therapeutic Efficacy of Human Adipose-Derived Stem Cells in a Murine Model of Multiple Sclerosis |
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| المؤلفون: | Umberto M. Donato, Sarah J. Aleman, Rachel M. Wise, Emily R. Monaco, Bruce A. Bunnell, Amber T. Vinluan, India A. Pursell, Sara Al-Ghadban, Brianne N. Sullivan, Mark Harrison |
| المصدر: | Cells Volume 9 Issue 10 Cells, Vol 9, Iss 2218, p 2218 (2020) |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | endocrine system, Multiple Sclerosis, medicine.medical_treatment, animal diseases, Adipose tissue, Inflammation, chemical and pharmacologic phenomena, Mesenchymal Stem Cell Transplantation, immunomodulation, Article, Paracrine signalling, Myelin, Mice, immune system diseases, adipose tissue-derived stem cells (ASCs), medicine, Animals, Humans, Rapamycin, lcsh:QH301-705.5, Sirolimus, business.industry, Multiple sclerosis, Experimental autoimmune encephalomyelitis, Mesenchymal Stem Cells, hemic and immune systems, General Medicine, medicine.disease, eye diseases, experimental autoimmune encephalomyelitis (EAE), Anti-Bacterial Agents, Disease Models, Animal, Cytokine, medicine.anatomical_structure, multiple sclerosis (MS), lcsh:Biology (General), inflammation, Cancer research, demyelination, Stem cell, medicine.symptom, business |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2073-4409 |
| DOI: | 10.3390/cells9102218 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d8f3cc4365f2d0f04ebbcc4e83ec0999Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d8f3cc4365f2d0f04ebbcc4e83ec0999 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20734409 |
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| DOI: | 10.3390/cells9102218 |