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Abstract：
In vitro surrogate models of human erythropoiesis made many contributions to our understanding of the extrinsic and intrinsic regulation of this process in vivo and how they are altered in erythroid disorders. In the past, variability among the levels of hemoglobin F produced by adult erythroblasts generated in vitro by different laboratories identified stage of maturation, fetal bovine serum, and accessory cells as \"confounding factors,\" that is, parameters intrinsically wired in the experimental approach that bias the results observed. The discovery of these factors facilitated the identification of drugs that accelerate terminal maturation or activate specific signaling pathways for the treatment of hemoglobinopathies. It also inspired studies to understand how erythropoiesis is regulated by macrophages present in the erythroid islands. Recent cell culture advances have greatly increased the number of human erythroid cells that can be generated in vitro and are used as experimental models to study diseases, such as Diamond Blackfan Anemia, which were previously poorly amenable to investigation. However, in addition to the confounding factors already identified, improvement in the culture models has introduced novel confounding factors, such as possible interactions between signaling from cKIT, the receptor for stem cell factor, and from the glucocorticoid receptor, the cell proliferation potential and the clinical state of the patients. This review will illustrate these new confounding factors and discuss their clinical translation potential to improve our understanding of Diamond Blackfan Anemia and other erythroid disorders. Stem Cells 2018;36:172-179.
摘要：
人类红细胞生成的体外替代模型为我们理解体内该过程的外在和内在调节以及它们在红系疾病中的变化做出了许多贡献。在过去,不同实验室确定的成熟阶段在体外产生的成年成红细胞产生的血红蛋白F水平之间的差异，胎牛血清,和附属细胞作为混杂因素，“也就是说，参数在实验方法中固有布线，使观察到的结果产生偏差。这些因素的发现有助于鉴定加速终末成熟或激活治疗血红蛋白病的特定信号通路的药物。它还启发了研究，以了解红细胞生成如何受到红细胞岛中存在的巨噬细胞的调节。最近的细胞培养进步大大增加了可以在体外产生的人类红系细胞的数量，并将其用作研究疾病的实验模型，比如DiamondBlackfan贫血,以前不太适合调查。然而,除了已经确定的混杂因素，文化模型的改进引入了新的混杂因素，例如来自cKIT的信令之间可能的相互作用，干细胞因子的受体，糖皮质激素受体，细胞增殖潜能和患者的临床状态。这篇综述将说明这些新的混杂因素，并讨论其临床翻译潜力，以提高我们对DiamondBlackfan贫血和其他红系疾病的理解。干细胞2018；36：172-179。
