Kirby S, Walton W, Smithies O
Department of Medicine, the Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7295, USA.
Blood. 2000 Jun 15;95(12):3710-5.
In a previous study, it was found that a truncated erythropoietin receptor transgene (tEpoR tg) enables multilineage hematopoietic progenitor amplification after treatment with erythropoietin (epo) in vitro and in vivo. This study used competitive bone marrow (BM) repopulation to show that tEpoR tg facilitates transplantation by hematopoietic stem cells (HSC). Individual multilineage colonies, committed myeloid progenitor colonies, and lymphoid colonies (pre-B colony-forming units) were grown from the marrow of animals 6 months after they received a 50/50 mixture of transgene and wild-type BM cells. In epo-treated recipients, the transgene-bearing cells significantly outcompeted the wild-type cells (84%-100% versus 16%-0%, respectively). In recipients treated with phosphate-buffered saline, the repopulation was minimally different from the donor mixture (49%-64% transgene versus 51%-36% wild-type). The epo-induced repopulation advantage is maintained in secondary transplants. In addition, neither accelerated HSC depletion nor uncontrollable proliferation occurred during epo-stimulated serial transplants of transgene-containing BM. Thus, the tEpoR tg functions in a benign fashion in HSC and allows for a significant and controllable repopulation advantage in vivo without excessive HSC depletion relative to wild-type BM. (Blood. 2000;95:3710-3715)
在先前的一项研究中，发现截短的促红细胞生成素受体转基因（tEpoR tg）在体外和体内经促红细胞生成素（epo）处理后能使多谱系造血祖细胞扩增。本研究采用竞争性骨髓（BM）重建来表明tEpoR tg促进造血干细胞（HSC）的移植。在接受转基因和野生型BM细胞50/50混合物的动物6个月后，从其骨髓中培养出单个多谱系集落、定向髓系祖细胞集落和淋巴样集落（前B集落形成单位）。在经epo处理的受体中，携带转基因的细胞显著胜过野生型细胞（分别为84% - 100%对16% - 0%）。在用磷酸盐缓冲盐水处理的受体中，重建情况与供体混合物的差异极小（转基因占49% - 64%，野生型占51% - 36%）。epo诱导的重建优势在二次移植中得以维持。此外，在含转基因BM的epo刺激的系列移植过程中，既未发生加速的HSC耗竭，也未出现不可控的增殖。因此，tEpoR tg在HSC中以良性方式发挥作用，在体内具有显著且可控的重建优势，相对于野生型BM而言不会导致过度的HSC耗竭。（《血液》。2000年；95:3710 - 3715）
