Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118, USA.
Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Cells. 2020 Sep 30;9(10):2218. 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.
人脂肪来源的干细胞（ASCs）在治疗炎症性疾病方面显示出巨大的潜力，这主要归因于其强大的旁分泌信号。先前的研究表明，短期雷帕霉素预处理骨髓来源的干细胞（BMSCs）可提高前列腺素 E2 的分泌，前列腺素 E2 是一种具有多发性硬化症（MS）实验性自身免疫性脑脊髓炎（EAE）模型治疗作用的多效分子，并增强体外免疫抑制能力。然而，这尚未在 ASCs 中进行研究。本研究探讨了短期雷帕霉素预处理 ASCs 在 EAE 模型中的治疗潜力。在疾病高峰期，用对照 ASCs（EAE-ASCs）、雷帕霉素预处理的 ASCs（EAE-Rapa-ASCs）或载体对照（EAE）治疗动物。结果表明，与 EAE 和 EAE-Rapa-ASC 动物相比，EAE-ASCs 改善了临床疾病评分并提高了完整髓鞘。这些结果与脊髓中 CD4 T 辅助（T）和 T 调节（T）细胞群体的增加以及抗炎细胞因子白细胞介素 10（IL-10）的基因表达相关。相反，EAE-Rapa-ASC 小鼠的临床疾病评分无改善，髓鞘水平降低，脊髓中的 T 和 T 细胞明显减少。这些发现表明，短期雷帕霉素预处理会降低晚期 EAE 时 ASCs 的治疗效果。
