Preimplantation-stage stem cells induce long-term allogeneic graft acceptance without supplementary host conditioning
Preimplantation-stage stem cells induce long-term allogeneic graft acceptance without supplementary host conditioning
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DOI：
10.1038/nm0202-171
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发表时间：
2002-02-01
期刊：
影响因子：
82.9
通讯作者：
Binas, B
中科院分区：
文献类型：
--
作者：
Fändrich, F;Lin, XB;Binas, B
造血干细胞已成功用于多种啮齿动物和大型动物研究中的耐受诱导。然而，完全异基因骨髓或血源性干细胞的临床移植仍然与主要障碍相关，例如移植物抗宿主病或细胞减少性条件相关毒性。在这里，我们表明，当大鼠胚胎干细胞样细胞的WKY起源注射到完全MHC不匹配的DA大鼠门静脉内，他们永久植入（>150天），没有补充的主机空调。这种潜在的同种异体反应性免疫反应的偏离为第二组移植的WKY心脏同种异体移植物的长期移植物接受奠定了基础。移植物存活率与混合嵌合状态密切相关，这需要功能性胸腺宿主能力。我们的研究结果提供了一个理论基础，为使用预分化阶段的干细胞作为车辆在基因治疗和诱导长期移植物的接受。
Hematopoietic stem cells have been successfully employed for tolerance induction in a variety of rodent and large animal studies. However, clinical transplantation of fully allogeneic bone marrow or blood-borne stem cells is still associated with major obstacles, such as graft-versus-host disease or cytoreductive conditioning-related toxicity. Here we show that when rat embryonic stem cell-like cells of WKY origin are injected intraportally into fully MHC-mismatched DA rats, they engraft permanently (>150 days) without supplementary host conditioning. This deviation of a potentially alloreactive immune response sets the basis for long-term graft acceptance of second-set transplanted WKY cardiac allografts. Graft survival was strictly correlated with a state of mixed chimerism, which required functional thymic host competence. Our results provide a rationale for using preimplantation-stage stem cells as vehicles in gene therapy and for the induction of long-term graft acceptance.