Reproducible immortalization of erythroblasts from multiple stem cell sources provides approach for sustainable RBC therapeutics.
Reproducible immortalization of erythroblasts from multiple stem cell sources provides approach for sustainable RBC therapeutics.
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DOI：
10.1016/j.omtm.2021.06.002
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发表时间：
2021-09-10
期刊：
影响因子：
--
通讯作者：
Frayne J
中科院分区：
文献类型：
--
作者：
Daniels DE;Ferguson DCJ;Griffiths RE;Trakarnsanga K;Cogan N;MacInnes KA;Mordue KE;Andrienko T;Ferrer-Vicens I;Ramos Jiménez D;Lewis PA;Wilson MC;Canham MA;Kurita R;Nakamura Y;Anstee DJ;Frayne J
开发可靠的方法，在体外可持续生产红细胞，对于提供临床质量血液的替代来源至关重要，特别是对于具有罕见血型表型的个体。永生化红细胞祖细胞系是实现这一目标最有前途的新兴技术。我们之前从骨髓CD34+细胞中创造了红细胞BEL-A，与其他报道的细胞系相比，它具有更好的分化和去核潜力。在这项研究中，我们证明了我们的永生化方法对于从骨髓分化的红细胞和更容易获得的外周血和脐带血CD34+细胞是可复制的，始终产生具有类似改善的红细胞性能的系。对这些细胞系的广泛表征表明，它们能够准确地再现它们的原代细胞等同物，并为永生化提供了分子特征。此外，我们发现只有处于特定红细胞生成阶段的细胞，主要是原红细胞，才有可能永生。我们的方法为临床使用的红细胞的可持续供应提供了动力，并为健康和疾病中红细胞生成研究的模型细胞系统的生成提供了动力，同时也为操纵分子靶点提供了无限扩展窗口。在这里，Daniels等人展示了来自骨髓、外周血和脐带血CD34+细胞的红细胞的可复制的永生化，并揭示了永生化的分子特征。这种方法为临床使用的红细胞的可持续生产和细胞模型系统的生成提供了一步。
Developing robust methodology for the sustainable production of red blood cells in vitro is essential for providing an alternative source of clinical-quality blood, particularly for individuals with rare blood group phenotypes. Immortalized erythroid progenitor cell lines are the most promising emergent technology for achieving this goal. We previously created the erythroid cell line BEL-A from bone marrow CD34+ cells that had improved differentiation and enucleation potential compared to other lines reported. In this study we show that our immortalization approach is reproducible for erythroid cells differentiated from bone marrow and also from far more accessible peripheral and cord blood CD34+ cells, consistently generating lines with similar improved erythroid performance. Extensive characterization of the lines shows them to accurately recapitulate their primary cell equivalents and provides a molecular signature for immortalization. In addition, we show that only cells at a specific stage of erythropoiesis, predominantly proerythroblasts, are amenable to immortalization. Our methodology provides a step forward in the drive for a sustainable supply of red cells for clinical use and for the generation of model cellular systems for the study of erythropoiesis in health and disease, with the added benefit of an indefinite expansion window for manipulation of molecular targets. Here Daniels et al. demonstrate reproducible immortalization of erythroid cells derived from bone marrow and peripheral and cord blood CD34+ cells and reveal a molecular signature of immortalization. This methodology provides a step toward the sustainable production of red cells for clinical use and for the generation of cellular model systems.
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影响因子：
5.2
作者：
Leong, Wai Fook;Chau, Jenny Fung Ling;Li, Baojie
通讯作者：
Li, Baojie
影响因子：
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作者：
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影响因子：
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作者：
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Eto, Koji
影响因子：
2.4
作者：
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通讯作者：
Babbs, Christian
DOI：
10.1126/science.aad3312
发表时间：
2016-01-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Masuda T;Wang X;Maeda M;Canver MC;Sher F;Funnell AP;Fisher C;Suciu M;Martyn GE;Norton LJ;Zhu C;Kurita R;Nakamura Y;Xu J;Higgs DR;Crossley M;Bauer DE;Orkin SH;Kharchenko PV;Maeda T
通讯作者：
Maeda T