Duncan B W, Harrison M R, Crombleholme T M, Clemons G, Tavassoli M, Zanjani E D
Department of Surgery, University of California, San Francisco.
Exp Hematol. 1992 Mar;20(3):350-3.
We have previously reported the successful development of hematopoietic chimerism after the in utero transplantation of fetal hematopoietic stem cells (HSC) in rhesus monkeys (Macaca mulatta). These animals exhibit sustained engraftment without immunosuppression or graft-versus-host disease (GVHD). To assess the functional response of the donor-derived erythropoietic population, we assayed the relative expression of donor and recipient hematopoietic progenitors in chimeric monkeys before and after anemic stress. Anemia in our chimeric animals resulted in increased erythropoietin (EPO) production comparable to controls. This was accompanied by changes in erythroid progenitor profiles, again similar to controls. Chimeric animals demonstrated normal reticulocytosis and reconstituted their hematocrit after hemorrhage at the same rate as controls. The donor-derived erythropoietic population exhibited normal responses to recipient regulatory signals and did not seem to expand at the expense of other hematopoietic lineages. Thus the proportions of engraftment for the myeloid and erythroid precursors in bone marrow and for blood lymphocytes remained stable. Our results demonstrate that the in utero transplantation of fetal HSC results in stable engraftment of donor erythropoietic progenitors, which appear to be fully integrated within the recipient's regulatory system. The abnormalities reported in the postnatal transplantation setting can then be attributed to immunologic reactions requiring conditioning myeloablative regimens. Fetal transplantation bypasses all these factors.
我们之前曾报道过，在恒河猴（猕猴）子宫内移植胎儿造血干细胞（HSC）后，成功实现了造血嵌合体的发育。这些动物在没有免疫抑制或移植物抗宿主病（GVHD）的情况下表现出持续的植入。为了评估供体来源的红细胞生成群体的功能反应，我们检测了嵌合猴在贫血应激前后供体和受体造血祖细胞的相对表达。我们的嵌合动物贫血导致促红细胞生成素（EPO）产生增加，与对照组相当。这伴随着红系祖细胞谱的变化，同样与对照组相似。嵌合动物表现出正常的网织红细胞增多，并在出血后以与对照组相同的速度恢复其血细胞比容。供体来源的红细胞生成群体对受体调节信号表现出正常反应，似乎不会以牺牲其他造血谱系为代价而扩张。因此，骨髓中髓系和红系前体以及血液淋巴细胞的植入比例保持稳定。我们的结果表明，子宫内移植胎儿HSC可导致供体红细胞生成祖细胞的稳定植入，这些祖细胞似乎已完全整合到受体的调节系统中。那么，出生后移植环境中报道的异常情况可归因于需要进行清髓性预处理方案的免疫反应。胎儿移植绕过了所有这些因素。
