El-Badri N S, Wang B Y, Steele A, Marikar Y, Mizobe K, Good R A
Department of Pediatrics, All Children's Hospital, University of South Florida, St. Petersburg 33701, USA.
Transplantation. 2000 Sep 27;70(6):870-7. doi: 10.1097/00007890-200009270-00004.
We have previously shown successful engraftment of allogeneic hematopoietic stem cells (HSCs) when transplanted across the major histocompatibility antigen barriers if transplanted along with a preparation of facilitator cells (osteoblasts). We have investigated whether or not fully allogeneic HSCs from healthy mouse donors prevent the development of autoimmunities in the autoimmune-prone W/B F1 mice.
W/B F1 is a strain of mice that spontaneously develop autoimmunities, a coronary vascular disease, thrombocytopenia, and systemic lupus-like syndrome. The 6- to 8-week-old (before the onset of the disease) W/B F1 mice have been transplanted with either a preparation of HSCs alone, or along with facilitator cells from MHC-incompatible autoimmune-resistant BALB/c mice, then followed to determine longterm survival and whether or not they developed signs of the autoimmune disease.
The number of the transplanted HSCs acts as the determining factor in achieving successful and durable engraftment. Survival of the W/B F1 mice significantly improved by transplantation of increasing numbers of HSCs, either alone or along with facilitator cells. When W/B F1 mice were transplanted with 2-5 million HSCs, more than 1-year survival was 100%, all the transplanted mice were fully engrafted with allogeneic HSCs, and were free of signs of the autoimmune disease. Histological sections of the hearts, lungs, and kidneys of the transplanted mice showed absence of the autoimmune-associated pathology.
We thus report herein the successful prevention of autoimmune disease by transplantation of a sufficiently large number of purified fully allogeneic HSCs in W/B F1 mice.
我们之前已经表明，如果在移植时同时植入促细胞（成骨细胞），异基因造血干细胞（HSCs）在跨越主要组织相容性抗原屏障进行移植时能够成功植入。我们研究了来自健康小鼠供体的完全异基因造血干细胞是否能预防自身免疫易感性W/B F1小鼠自身免疫性疾病的发生。
W/B F1是一种会自发出现自身免疫性疾病、冠状动脉血管疾病、血小板减少症和系统性狼疮样综合征的小鼠品系。6至8周龄（疾病发作前）的W/B F1小鼠被移植了单独的造血干细胞制剂，或同时移植了来自MHC不相容的自身免疫抗性BALB/c小鼠的促细胞，然后对其进行跟踪以确定长期存活率以及它们是否出现自身免疫性疾病的迹象。
移植的造血干细胞数量是实现成功和持久植入的决定性因素。通过移植数量不断增加的造血干细胞，无论单独移植还是与促细胞一起移植，W/B F1小鼠的存活率都显著提高。当给W/B F1小鼠移植200万至500万个造血干细胞时，超过1年的存活率为100%，所有移植小鼠均被完全植入异基因造血干细胞，且无自身免疫性疾病迹象。移植小鼠心脏、肺和肾脏的组织学切片显示不存在与自身免疫相关的病理变化。
因此，我们在此报告，通过在W/B F1小鼠中移植足够数量的纯化完全异基因造血干细胞成功预防了自身免疫性疾病。
