Bachar-Lustig E, Rachamim N, Li H W, Lan F, Reisner Y
Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot, Israel.
Nat Med. 1995 Dec;1(12):1268-73. doi: 10.1038/nm1295-1268.
Graft-versus-host disease (GVHD) is uniformly lethal in recipients of HLA-mismatched marrow. In patients with severe combined immunodeficiency disease, this major obstacle can be overcome by rigorous T-cell depletion before transplantation. In leukaemia patients, however, the benefit of preventing GVHD is offset by graft rejection or graft failure. Very recently, this problem was overcome by supplementing T cell-depleted bone marrow transplants with megadoses of peripheral blood stem cells collected by leukapheresis after mobilization of the donor stem cells with granulocyte colony-stimulating factor (G-CSF). In the present study, we further demonstrate in a mouse model (C57BL/6-->C3H/Hej) that escalation of bone marrow doses by four- to fivefold leads to full donor-type chimerism in sublethally irradiated (6.5 Gy) recipients. Thus, the new source of G-CSF mobilized human haematopoietic stem cells may enable extending the use of mismatched bone marrow transplants to patients with non-malignant diseases for whom supralethal conditioning is not a prerequisite.
移植物抗宿主病（GVHD）在接受HLA不匹配骨髓移植的受者中通常是致命的。在严重联合免疫缺陷病患者中，这一主要障碍可通过移植前严格的T细胞清除来克服。然而，在白血病患者中，预防GVHD的益处被移植物排斥或移植物衰竭所抵消。最近，通过用粒细胞集落刺激因子（G-CSF）动员供体干细胞后，通过白细胞分离术收集的超大剂量外周血干细胞补充T细胞清除的骨髓移植，这个问题得到了解决。在本研究中，我们在小鼠模型（C57BL/6→C3H/Hej）中进一步证明，将骨髓剂量增加四到五倍可导致亚致死剂量照射（6.5 Gy）的受者出现完全供体型嵌合体。因此，G-CSF动员的人类造血干细胞的新来源可能使不匹配骨髓移植能够扩展到非恶性疾病患者，而对于这些患者来说，超致死预处理并非必要条件。
