BEHAVIOR OF HEMATOPOIETIC STEM-CELLS IN A LARGE ANIMAL
BEHAVIOR OF HEMATOPOIETIC STEM-CELLS IN A LARGE ANIMAL
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DOI：
10.1073/pnas.92.6.2031
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发表时间：
1995-03-14
影响因子：
11.1
通讯作者：
GUTTORP, P
中科院分区：
文献类型：
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作者：
ABKOWITZ, JL;PERSIK, MT;GUTTORP, P
为了研究造血干细胞在体内的行为，我们将葡萄糖-6-磷酸脱氢酶（G6PD）杂合（雌性Safari）猫与少量自体骨髓移植。在移植后的3.5-6年里，反复检测红细胞爆发形成单位和粒细胞/巨噬细胞集落形成单位的G6PD表型，以追踪干细胞克隆对祖细胞室的贡献。观察到干细胞动力学的两个阶段，这与在可比的小鼠研究中报道的模式相似。最初，干细胞克隆的贡献有很大的波动。后来克隆对造血的贡献趋于稳定。然而，锥体不平衡的初始阶段延长了1-4.5年（而不是在小鼠实验中看到的2-6个月）。在这种情况消退后，来自一些动物的所有祖细胞都表达单一亲本G6PD表型，这表明一个（或几个）细胞的后代可以稳定地维持血细胞的产生。由于猫的造血需求（即一生中产生的血细胞数量）是老鼠的600多倍，这提供了单个造血干细胞具有巨大的自我更新和/或增殖能力的证据。克隆不稳定的长阶段可能反映了干细胞充分复制以重建大量干细胞储备所需的时间。
To study the behavior of hematopoietic stem cells in vivo, we transplanted glucose-6-phosphate dehydrogenase (G6PD) heterozygous (female Safari) cats with small amounts of autologous marrow. The G6PD phenotypes of erythroid burst-forming units and granulocyte/macrophage colony-forming units were repeatedly assayed for 3.5-6 years after transplantation to track contributions of stem cell clones to the progenitor cell compartment. Two phases of stem cell kinetics were observed, which were similar to the pattern reported in comparable murine studies. Initially there were significant fluctuations in contributions of stem cell clones. Later clonal contributions to hematopoiesis stabilized. The initial phase of conal disequilibrium, however, extended for 1-4.5 years (and not 2-6 months as seen in murine experiments). After this subsided, all progenitor cells from some animals expressed a single parental G6PD phenotype, suggesting that blood cell production could be stably maintained by the progeny of one (or a few) cells. As the hematopoietic demand of a cat (i.e., number of blood cells produced per lifetime) is over 600 times that of a mouse, this provides evidence that an individual hematopoietic stem cell has a vast self-renewal and/or proliferative capacity. The long phase of clonal instability may reflect the time required for stem cells to replicate sufficiently to reconstitute a large stem cell reserve.