Experimental allergic encephalomyelitis (EAE) is the animal model of multiple sclerosis (MS). Autologous hematopoietic stem cell transplantation (AHSCT) has recently been recognized as the standard treatment for MS. The aim of our experiment was to investigate the effect of AHSCT with the addition of low-dose post-transplantation cyclophosphamide (Cy) on EAE in rats. Low dose post-transplantation Cy is used in haploidentical HSCT to reduce the risk of graft versus host disease. We hypothesized that it could bring additional benefit in autologous HSCT in autoimmune diseases. Rats with evoked EAE were treated with high dose (125 mg/kg) Cy, followed by AHSCT or high dose (125 mg/kg) Cy followed by AHSCT followed by low dose (20 mg/kg) Cy in two-time schedules—with the therapy applied during the pre-symptomatic or symptomatic phase of the disease. Both AHSCT and AHSCT with post-transplantation Cy in accordance with both time schedules reduce the intensity of the inflammatory response in the CNS, in comparison with non-treated EAE rats. The reduction of clinical symptoms was present in all AHSCT treatment protocols, however, it was significantly stronger when post-transplantation Cy was given during the symptomatic phase of the disease. AHSCT with the addition of post HSCT low dose Cy improved the results of AHSCT by not only reducing the intensity of inflammation in the CNS but also by significantly reducing the clinical symptoms in treated animals when compared to AHSCT alone. We provide an experimental rationale that the addition of post-transplantation Cy may improve the outcome of HSCT in MS.

Graphic Abstract

中文翻译：

---

移植后环磷酰胺改善多发性硬化动物模型自体造血干细胞移植的结果

实验性过敏性脑脊髓炎 (EAE) 是多发性硬化症 (MS) 的动物模型。自体造血干细胞移植 (AHSCT) 最近被认为是 MS 的标准治疗方法。我们实验的目的是研究 AHSCT 加入低剂量移植后环磷酰胺 (Cy) 对大鼠 EAE 的影响。低剂量移植后 Cy 用于半相合 HSCT 以降低移植物抗宿主病的风险。我们假设它可以为自身免疫性疾病的自体 HSCT 带来额外的好处。诱发 EAE 的大鼠用高剂量 (125 mg/kg) Cy 治疗，然后是 AHSCT 或高剂量 (125 mg/kg) Cy，然后是 AHSCT，然后是低剂量 (20 mg/kg) Cy，分两次计划——在疾病的症状前或症状阶段应用治疗。与未治疗的 EAE 大鼠相比，AHSCT 和具有移植后 Cy 的 AHSCT 根据两个时间表都降低了 CNS 中的炎症反应强度。在所有 AHSCT 治疗方案中都存在临床症状的减轻，但是，在疾病的症状阶段给予移植后 Cy 时，临床症状的减轻明显更强。与单独的 AHSCT 相比，添加 HSCT 后低剂量 Cy 的 AHSCT 不仅通过降低 CNS 中的炎症强度而且通过显着减少治疗动物的临床症状来改善 AHSCT 的结果。我们提供了一个实验原理，即添加移植后 Cy 可能会改善 MS 中 HSCT 的结果。

图形摘要