Establishment of immortalized human erythroid progenitor cell lines able to produce enucleated red blood cells.

Establishment of immortalized human erythroid progenitor cell lines able to produce enucleated red blood cells.
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DOI:
10.1371/journal.pone.0059890
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Nakamura Y
Nakamura Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kurita R;Suda N;Sudo K;Miharada K;Hiroyama T;Miyoshi H;Tani K;Nakamura Y

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输注红细胞(RBC)是目前临床实践中标准且不可或缺的治疗方法。RBC的体外生产提供了一种潜在的手段,以克服在某些临床情况下可替代的RBC的短缺,并且还提供了不受微生物感染或污染的细胞来源。因此,在体外生产红细胞可能成为未来的标准程序。我们先前报道了永生化小鼠红系祖细胞系的成功建立,该细胞系能够非常有效地产生成熟的RBC。在这里,我们已经开发了一个可靠的协议,建立永生化人红系祖细胞系,能够产生去核红细胞。这些永生化细胞系产生功能性血红蛋白并表达红系特异性标志物,并且这些标志物在体外诱导分化后上调。最重要的是,这些永生化细胞系在体外诱导分化后均产生去核RBC,尽管产生去核RBC的效率仍有待进一步提高。据我们所知,这是第一次证明使用永生化人红系祖细胞系作为生产去核RBC的离体来源的可行性。
Transfusion of red blood cells (RBCs) is a standard and indispensable therapy in current clinical practice. In vitro production of RBCs offers a potential means to overcome a shortage of transfusable RBCs in some clinical situations and also to provide a source of cells free from possible infection or contamination by microorganisms. Thus, in vitro production of RBCs may become a standard procedure in the future. We previously reported the successful establishment of immortalized mouse erythroid progenitor cell lines that were able to produce mature RBCs very efficiently. Here, we have developed a reliable protocol for establishing immortalized human erythroid progenitor cell lines that are able to produce enucleated RBCs. These immortalized cell lines produce functional hemoglobin and express erythroid-specific markers, and these markers are upregulated following induction of differentiation in vitro. Most importantly, these immortalized cell lines all produce enucleated RBCs after induction of differentiation in vitro, although the efficiency of producing enucleated RBCs remains to be improved further. To the best of our knowledge, this is the first demonstration of the feasibility of using immortalized human erythroid progenitor cell lines as an ex vivo source for production of enucleated RBCs.
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