Thymus transplantation, a critical factor for correction of autoimmune disease in aging MRL/+ mice
Thymus transplantation, a critical factor for correction of autoimmune disease in aging MRL/+ mice
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DOI：
10.1073/pnas.93.16.8558
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发表时间：
1996-08-06
影响因子：
11.1
通讯作者：
Ikehara, S
中科院分区：
文献类型：
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作者：
Hosaka, N;Nose, M;Ikehara, S
MRL/MP-+/+(MRL/+)小鼠在7个月龄后发生胰腺炎和涎腺炎。传统的骨髓移植已被发现在治疗这些明显的自身免疫性疾病方面无效。随着年龄的增长，老年MRL/+小鼠表现出戏剧性的胸腺退化。当胎肝细胞(作为造血干细胞的来源)和胎骨(用于招募基质细胞)从免疫正常的C57BL/6供体小鼠移植到MRL/+女性受者身上时，血淋巴重建是不完整的。因此，来自异基因C57BL/6捐赠者的胚胎胸腺与骨髓或胎儿造血细胞(FHC)加上成人或胎儿骨骼的碎片一起植入。超过70%的老年MRL/+小鼠(7个月)接受了胎儿胸腺(FT)移植加上骨髓或FHC以及骨碎片治疗后存活超过100天。接受来自异基因供者的FHC、FB和FT的小鼠发展为正常的T细胞和B细胞功能。这些小鼠的血清淀粉酶水平降低，而接受FHC和FB但不接受FT的小鼠血清淀粉酶水平升高。移植时已经存在的胰腺炎和涎腺炎根据组织学分析通过移植同种异体FHC、FB和FT在MRL/+小鼠中得到完全纠正。这些发现被认为是一个实验迹象，表明干细胞移植和FT移植可能是治疗老年人自身免疫性疾病的一种有用的策略。
MRL/MP-+/+ (MRL/+) mice develop pancreatitis and sialoadenitis after they reach 7 months of age. Conventional bone marrow transplantation has been found to be ineffective in the treatment of these forms of apparent autoimmune disease. Old MRL/+ mice show a dramatic thymic involution with age. Hematolymphoid reconstitution is incomplete when fetal liver cells (as a source of hemopoietic stem cells) plus fetal bone (FB; which is used to recruit stromal cells) are transplanted from immunologically normal C57BL/6 donor mice to MRL/+ female recipients. Embryonic thymus from allogeneic C57BL/6 donors was therefore engrafted along with either bone marrow or fetal hematopoietic cells (FHCs) plus fragments of adult or fetal bone. More than seventy percent of old MRL/+ mice (>7 months) that had been given a fetal thymus (FT) transplant plus either bone marrow or FHCs and also bone fragments survived more than 100 days after treatment. The mice that received FHCs, FB, plus FT from allogeneic donors developed normal T cell and B cell functions. Serum amylase levels decreased in these mice whereas they increased in the mice that received FHCs and FB but not FT. The pancreatitis and sialoadenitis already present at the time of transplantations were fully corrected according to histological analysis by transplants of allogeneic FHCs, FB and FT in the MRL/+ mice. These findings are taken as an experimental indication that perhaps stem cell transplants along with FT grafts might represent a useful strategy for treatment of autoimmune diseases in aged humans.