van Bekkum D W
Crucell B.V., Leiden, The Netherlands.
J Leukoc Biol. 2002 Oct;72(4):609-20.
Experiments with animal models of autoimmune disease provided the rational and stimulus for the current, clinical studies of autologous stem cell transplantation for the treatment of a variety of severe, refractory, autoimmune diseases. The discoveries that led to the recognition of the key role of hematopoietic stem cells and the successful treatment of autoimmune diseases with bone marrow transplants are reviewed. The relevance of spontaneous and induced autoimmune disease models for the development of clinical treatment regimens is discussed. Most of the investigations with autologous stem cell transplantation have been performed with induced autoimmune disorders: in rats with adjuvant arthritis and in rats or mice with experimental, allergic encephalomyelitis, the current model for multiple sclerosis. The main aspects of this translational research were the conditioning regimens and the degree of T cell depletion of the graft as determinants of remission induction and the incidence of relapses. The emerging recommendations are compared with the outcome so far of the clinical studies.
自身免疫性疾病动物模型实验为当前自体干细胞移植治疗各种严重、难治性自身免疫性疾病的临床研究提供了理论依据和动力。本文回顾了促成人们认识造血干细胞关键作用以及通过骨髓移植成功治疗自身免疫性疾病的各项发现。讨论了自发和诱导性自身免疫性疾病模型在临床治疗方案开发中的相关性。大多数自体干细胞移植研究是在诱导性自身免疫性疾病模型中进行的：在佐剂性关节炎大鼠以及实验性变应性脑脊髓炎大鼠或小鼠（目前用于多发性硬化症的模型）中进行。这项转化研究的主要方面是预处理方案以及移植物中T细胞清除程度，它们是诱导缓解和复发率的决定因素。将新出现的建议与目前临床研究的结果进行了比较。
