Post Transplantation Cyclophosphamide Improves Outcome of Autologous Hematopoietic Stem Cell Transplantation in Animal Model of Multiple Sclerosis

IF 2.9 4区医学 Q3 IMMUNOLOGY

Archivum Immunologiae et Therapiae Experimentalis Pub Date : 2021-06-28 DOI:10.1007/s00005-021-00619-4

Kaja Kasarełło, Emilian Snarski, Dorota Sulejczak, Tomasz Ciesielski, Agnieszka Wiśniewska, Robert Wrzesień, Agnieszka Cudnoch-Jędrzejewska

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引用次数: 1

Abstract

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

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移植后环磷酰胺改善多发性硬化症动物模型自体造血干细胞移植的预后

实验性变态反应性脑脊髓炎（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与低剂量移植后环磷酰胺（Cy）的联合对大鼠EAE的影响。低剂量移植后Cy用于单倍体HSCT，以降低移植物抗宿主疾病的风险。我们假设它可以为自身免疫性疾病的自体HSCT带来额外的益处。对诱发EAE的大鼠采用高剂量（125 mg/kg）Cy，然后进行AHSCT或高剂量（125mg/kg）Cys，然后AHSCT，然后低剂量（20mg/kg）Cy的两个时间方案进行治疗，治疗在疾病的症状前或症状期进行。与未经治疗的EAE大鼠相比，AHSCT和移植后Cy符合两个时间表的AHSCT都降低了中枢神经系统炎症反应的强度。临床症状的减轻在所有AHSCT治疗方案中都存在，然而，当在疾病的症状阶段给予移植后Cy时，这种减轻明显更强。与单独AHSCT相比，添加HSCT后低剂量Cy的AHSCT不仅降低了中枢神经系统的炎症强度，而且显著降低了治疗动物的临床症状，从而改善了AHSCT的结果。我们提供了一个实验依据，即移植后添加Cy可以改善MS中HSCT的结果。图片摘要

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来源期刊

Archivum Immunologiae et Therapiae Experimentalis 医学-免疫学

CiteScore

5.90

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Archivum Immunologiae et Therapiae Experimentalis (AITE), founded in 1953 by Ludwik Hirszfeld, is a bimonthly, multidisciplinary journal. It publishes reviews and full original papers dealing with immunology, experimental therapy, immunogenetics, transplantation, microbiology, immunochemistry and ethics in science.