During the last years, several strategies have been made to obtain mature erythrocytes or red blood cells (RBC) from the bone marrow or umbilical cord blood (UCB). However, UCB-derived hematopoietic stem cells (HSC) are a limited source and in vitro large-scale expansion of RBC from HSC remains problematic. One promising alternative can be human pluripotent stem cells (PSCs) that provide an unlimited source of cells. Human PSCs, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), are self-renewing progenitors that can be differentiated to lineages of ectoderm, mesoderm, and endoderm. Several previous studies have revealed that human ESCs can differentiate into functional oxygen-carrying erythrocytes; however, the ex vivo expansion of human ESC-derived RBC is subjected to ethical concerns. Human iPSCs can be a suitable therapeutic choice for the in vitro/ex vivo manufacture of RBCs. Reprogramming of human somatic cells through the ectopic expression of the transcription factors (OCT4, SOX2, KLF4, c-MYC, LIN28, and NANOG) has provided a new avenue for disease modeling and regenerative medicine. Various techniques have been developed to generate enucleated RBCs from human iPSCs. The in vitro production of human iPSC-derived RBCs can be an alternative treatment option for patients with blood disorders. In this review, we focused on the generation of human iPSC-derived erythrocytes to present an overview of the current status and applications of this field.

中文翻译：

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人诱导多能干细胞分化为红系细胞

在过去的几年中，已经采取了几种策略来从骨髓或脐带血（UCB）获得成熟的红细胞或红细胞（RBC）。然而，来自UCB的造血干细胞（HSC）是有限的来源，并且来自HSC的RBC的体外大规模扩增仍然是有问题的。一种有前途的替代方案可以是提供多种细胞来源的人多能干细胞（PSC）。人类PSC，包括胚胎干细胞（ESC）和诱导性多能干细胞（iPSC），是可以自我更新的祖细胞，可以分化为外胚层，中胚层和内胚层谱系。先前的一些研究表明，人类胚胎干细胞可以分化为功能性的携氧红细胞。然而，人类ESC衍生的RBC的离体扩增受到伦理学的关注。人iPSC可能是体外/离体制造RBC的合适治疗选择。通过转录因子（OCT4，SOX2，KLF4，c-MYC，LIN28和NANOG）的异位表达对人类体细胞进行重编程，为疾病建模和再生医学提供了新途径。已经开发出多种技术来从人iPSC产生去核的RBC。人iPSC衍生的RBC的体外生产可以作为血液疾病患者的另一种治疗选择。在这篇综述中，我们专注于人类iPSC衍生的红细胞的产生，以概述该领域的现状和应用。c-MYC，LIN28和NANOG）为疾病建模和再生医学提供了新途径。已经开发出多种技术来从人iPSC产生去核的RBC。人iPSC衍生的RBC的体外生产可以作为血液疾病患者的另一种治疗选择。在这篇综述中，我们专注于人类iPSC衍生的红细胞的产生，以概述该领域的现状和应用。c-MYC，LIN28和NANOG）为疾病建模和再生医学提供了新途径。已经开发出多种技术来从人iPSC产生去核的RBC。人iPSC衍生的RBC的体外生产可以作为血液疾病患者的另一种治疗选择。在这篇综述中，我们专注于人类iPSC衍生的红细胞的产生，以概述该领域的现状和应用。