Barker J E, McFarland E
Blood. 1985 Sep;66(3):595-601.
The alpha-thalassemic mouse has a hereditary microcytic anemia, almost certainly has a shortened RBC life span, and is a potential candidate for cell replacement therapy. In a routine study of bone marrow repopulating capacity using hemoglobin as a cell marker, normal donor marrow cells, but not alpha-thalassemic donor marrow cells, completely replaced the host cells. Further analysis showed that at least 30 times more alpha-thalassemic cells were required to outcompete normal donor cells injected simultaneously. The results were more extreme then expected and suggested a defect in a stem cell population as well as in the RBCs. Evidence that the multipotent and erythroid-committed stem cells in alpha-thalassemic mice are not decreased was shown by CFU-S and CFU-E assays. The combined results indicate that the deletion expresses itself most conspicuously in the RBC population. Tests were also performed to analyze repopulation kinetics in the Hbath-J/+ mice. In unirradiated alpha-thalassemic hosts, the hemoglobin from a normal donor persisted but did not replace the host hemoglobin. Sublethally irradiated alpha-thalassemic hosts, on the other hand, were easily repopulated with normal cells. We conclude that the alpha-thalassemic mouse is a good model for cell replacement therapy.
α地中海贫血小鼠患有遗传性小细胞贫血，几乎可以肯定其红细胞寿命缩短，是细胞替代疗法的潜在候选对象。在一项以血红蛋白作为细胞标志物对骨髓重建能力进行的常规研究中，正常供体骨髓细胞而非α地中海贫血供体骨髓细胞完全替代了宿主细胞。进一步分析表明，要超过同时注射的正常供体细胞，α地中海贫血细胞的数量至少需要多出30倍。结果比预期更为极端，提示干细胞群体以及红细胞存在缺陷。CFU-S和CFU-E检测表明，α地中海贫血小鼠中的多能干细胞和红细胞定向干细胞并未减少。综合结果表明，该缺失在红细胞群体中表现最为明显。还进行了测试以分析Hbath-J/+小鼠的重建动力学。在未受辐射的α地中海贫血宿主中，正常供体的血红蛋白持续存在，但并未替代宿主血红蛋白。另一方面，接受亚致死剂量辐射的α地中海贫血宿主很容易被正常细胞重建。我们得出结论，α地中海贫血小鼠是细胞替代疗法的良好模型。
