Allogeneic bone marrow transplantation in irradiated adult rabbits.
Allogeneic bone marrow transplantation in irradiated adult rabbits.
复制标题
受辐射成年兔的同种异体骨髓移植。
DOI：
10.1097/00007890-198709000-00005
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发表时间：
1987
期刊：
影响因子：
6.2
通讯作者：
Appelbaum,FR
中科院分区：
文献类型：
--
作者：
Bigelow,CL;Adler,LT;Appelbaum,FR
为了在不相关的RA匹配的成年兔中产生稳定的、长期的、完全的造血嵌合体，定义了在有和没有自体骨髓支持的情况下全身照射（TBI）的最大耐受剂量，然后确定最大耐受剂量是否具有足够的免疫抑制和清髓性以允许同种异体骨髓的植入。40只家兔接受4、8 cGy/min的TBI，剂量范围为525-925 cGy。接受525、625、725和825 cGy剂量的家兔均存活，无骨髓移植。在875 cGy时，50%的动物死亡，在925 cGy时，所有动物在TBI后96小时内死亡。自体骨髓支持的存活率没有改变，所有接受825 cGy的动物都存活了下来，而875 cGy的存活率为50%，925 cGy的存活率为零。在825 cGy照射后，对两个RLA匹配、性别和免疫球蛋白同种异型不匹配的配对进行了移植，并在移植后给予环孢霉素。两名受者在移植后均存活超过200天，细胞遗传学和免疫球蛋白同种异型证据表明完全或接近完全造血植入。因此，用TBI法制备的HLA相合的成年无血缘关系的家兔可获得稳定的、长期的完全嵌合体，这种动物模型可用于骨髓移植研究，其移植骨髓的能力已被发现有许多临床用途。对于再生障碍性贫血、地中海贫血或其他非恶性骨髓疾病的患者，骨髓移植已被证明具有治疗潜力（1，2）。骨髓移植也提供了一种克服常规放化疗剂量限制性毒性的方法，允许提供更高的剂量。这种方法提供了一种治愈患有其他不可治愈的恶性血液病的患者的方法，包括慢性髓细胞性白血病，复发性急性白血病和恶性淋巴瘤（3，4）。骨髓移植也被用于治疗涉及非造血细胞以及造血细胞的代谢疾病（5，6）。在这种情况下，骨髓移植为缺陷患者提供了正常移植骨髓中正常酶或受体的来源。对近交系啮齿动物的研究为骨髓移植的免疫遗传学提供了许多基础知识。然而，获得的一些信息很难转移到人类，一个随机繁殖的物种。较大的哺乳动物，如
In an effort to produce stable, long-term, complete hematopoietic chimerism in unrelated RLA-matched adult rabbits, the maximum dose of total-body irradiation (TBI) tolerated both with and without autologous marrow support was defined, and it was then deter-mined whether the maximum tolerated dose was suffi-ciently immunosuppressive and myeloablative to allow engraftment of allogeneic marrow. Forty rabbits received TBI at 4, 8 cGy/min at doses from 525-925 cGy. All rabbits receiving 525, 625, 725 and 825 cGy sur-vived without marrow transplantation. At 875 cGy 50% of animals died and at 925 cGy all animals died within 96 hr of TBI. Survival was not changed with autologous marrow support, with all animals receiving 825 cGy surviving, while 50% survived at 875 cGy, and none at 925 cGy. Two RLA-matched, sex and immunoglobulin allotype-mismatched pairs were transplanted following 825 cGy and were given posttransplant cyclosporine. Both recipients survived beyond 200 days posttransplant, with cytogenetic and immunoglobulin allotype evidence of complete, or nearly complete, hematopoietic engraftment. Thus, stable, long-term complete chimer-ism can be achieved in adult RLA-matched unrelated rabbits prepared by TBI, and this animal model can be used for bone marrow transplantation studies.The ability to transplant marrow has found a number of clinical uses. In patients with aplastic anemia, thalassemia, or other nonmalignant disorders of the marrow, bone marrow transplantation has demonstrated curative potential (1, 2). Marrow transplantation also provides a means of overcoming the usual dose-limiting toxicity of chemoradiotherapy, allowing the delivery of higher doses. This approach provides a means of curing patients with otherwise incurable hematologic malignancies, including chronic myelogenous leukemia, relapsed acute leukemia, and malignant lymphoma (3, 4). Marrow transplantation has also been used to treat metabolic disorders involving nonhematopoietic, as well as hematopoietic, cells (5, 6). In this setting, marrow transplantation provides the deficient patient with a source of normal enzymes or receptors in the normal transplanted marrow. Studies in inbred rodents have provided much of the basic knowledge of the immunogenetics of marrow transplantation. However, some of the information obtained is difficult to transfer to man, a random-bred species. Larger mammals such as