CD34+ marrow cells, devoid of T and B lymphocytes, reconstitute stable lymphopoiesis and myelopoiesis in lethally irradiated allogeneic baboons

CD34+ marrow cells, devoid of T and B lymphocytes, reconstitute stable lymphopoiesis and myelopoiesis in lethally irradiated allogeneic baboons
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CD34 骨髓细胞缺乏 T 和 B 淋巴细胞,在受到致命辐射的同种异体狒狒中重建稳定的淋巴细胞生成和骨髓生成

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发表时间:
1992
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影响因子:
--
通讯作者:
I. Bernstein
I. Bernstein
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文献类型:
--
作者:
R. Andrews;E. Bryant;S. Bartelmez;D. Muirhead;G. Knitter;W. Bensinger;D. Strong;I. Bernstein

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从三对性别不匹配、混合淋巴细胞培养(MLC)无反应性的同胞狒狒骨髓中分离出表达CD 2、CD 10和CD 20抗原的CD 34+细胞(不含可检测到的成熟和未成熟T和B淋巴细胞)。在每对的成员之间进行相互移植,使用性染色体,通过标准细胞遗传学技术鉴定,作为移植细胞的标记。对这三对中的五只动物移植0.6至2.1 x 10(6)/kg的分离的冻存和/或新鲜分离的细胞,这些细胞的CD 34+大于95%至97%。在移植前,动物接受单次(920或1,020 cGy)或分次(700 cGy x 2)剂量全身照射。移植后4周骨髓中期细胞的细胞遗传学分析表明,所有移植供体细胞的动物,至白色血细胞计数(WBC)大于500的天数为19 +/- 2,至WBC大于1,000的天数为23 +/- 2,至中性粒细胞绝对计数大于500的天数为24 +/- 3,以及至血小板大于20的天数,000 30 +/- 7。三只动物在移植后34、42和109天死于感染相关并发症,骨髓中存在宿主和供体细胞(混合嵌合体)的证据。两个动物在移植后存活和健康超过545和455天,在骨髓和血液中具有稳定的混合嵌合体。对于这两只动物,移植后25周至42周之间骨髓前体细胞来源的粒细胞/巨噬细胞和红细胞集落的细胞遗传学分析显示混合嵌合体的证据。从移植后21周至51周这两只动物血液中分离的CD 2 + T细胞和CD 20 + B细胞的细胞遗传学研究显示,两种淋巴细胞群中均存在混合嵌合体。因此,分离的同种异体CD 34+骨髓细胞(不含可检测到的成熟和未成熟T淋巴细胞和B淋巴细胞)可在致死性辐照狒狒中移植并重建稳定的长期骨髓生成和淋巴生成。这些结果与CD 34+骨髓细胞含有能够在移植宿主中完全重建淋巴造血的多能造血干细胞的假设一致。
CD34+ cells devoid of detectable mature and immature T and B lymphocytes, expressing the CD2, CD10, and CD20 antigens, were isolated from marrows of three pairs of sex-mismatched, mixed lymphocyte culture (MLC) nonreactive, sibling baboons. Reciprocal transplants were performed between members of each pair, using the sex chromosomes, identified by standard cytogenetic techniques, as markers of the transplanted cells. Five animals from these three pairs were transplanted with 0.6 to 2.1 x 10(6)/kg of isolated cryopreserved and/or fresh isolated cells that were greater than 95% to 97% CD34+. Before transplantation, animals were treated with either single (920 or 1,020 cGy) or split (700 cGy x 2) dose total body irradiation. All animals engrafted with donor cells, as demonstrated by cytogenetic analysis of bone marrow metaphase cells 4 weeks after transplantation, with days to white blood cell count (WBC) greater than 500 being 19 +/- 2, to WBC greater than 1,000 23 +/- 2, to absolute neutrophil count greater than 500 24 +/- 3, and to platelets greater than 20,000 30 +/- 7. Three animals died of infectious-related complications at 34, 42, and 109 days after transplantation with evidence of host and donor cells (mixed chimerism) in marrow. Two animals remain alive and healthy more than 545 and 455 days after transplantation with stable mixed chimerism in marrow and blood. For these two animals, cytogenetic analysis of granulocyte/macrophage and erythroid colonies derived from marrow precursors between weeks 25 and 42 posttransplant showed evidence of mixed chimerism. Cytogenetic studies of CD2+ T cells and CD20+ B cells isolated from blood of these two animals between weeks 21 and 51 posttransplant showed the presence of mixed chimerism in both lymphocyte populations. Thus, isolated allogeneic CD34+ marrow cells devoid of detectable mature and immature T and B lymphocytes can engraft and reconstitute stable long-term myelopoiesis and lymphopoiesis in lethally irradiated baboons. These results are consistent with the hypothesis that CD34+ marrow cells contain pluripotent hematopoietic stem cells capable of fully reconstituting lymphohematopoiesis in the transplanted host.
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发表时间: 1982
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