Long-lasting in vitro hematopoiesis derived from primate embryonic stem cells
Long-lasting in vitro hematopoiesis derived from primate embryonic stem cells
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DOI：
10.1016/j.exphem.2006.03.004
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发表时间：
2006-06-01
影响因子：
2.6
通讯作者：
Nakamura, Yukio
中科院分区：
文献类型：
--
作者：
Hiroyama, Takashi;Miharada, Kenichi;Nakamura, Yukio
Objective.近年来，从人胚胎干细胞（ES细胞）诱导造血细胞的报道越来越多。然而，在从人ES细胞衍生的细胞可用于临床之前，在实验灵长类动物中使用这些细胞的临床前研究将是必要的。因此，我们试图建立一种从灵长类ES细胞中稳健、大量诱导造血细胞的方法。本研究中使用了来自食蟹猴的灵长类动物ES细胞系CMK-6。我们采用饲养细胞诱导CMK-6细胞造血的方法，并测试了三种饲养细胞系（OP 9，C2 C1/2和C3 H10 T1/2）的有效性。此外，我们还检测了血管内皮生长因子（VEGF）和胰岛素样生长因子-II（IGF-II）对CMK-6细胞造血诱导的影响。VEGF和IGF-II显示出极强的协同作用，以诱导CMK-6细胞的造血。C3 H10 T1/2细胞对CMK-6细胞的造血诱导非常有用，并且在C3 H10 T1/2细胞上产生的血细胞已维持长达5个月。在此期间，ES细胞衍生物不断产生成熟的血细胞，包括终末分化细胞。我们已经开发出一种独特的方法，可以从灵长类动物的ES细胞中大量生产富集的血细胞。该方法为灵长类动物造血及相关疾病的研究提供了一个良好的体外模型。此外，我们的方法可能是有用的输血治疗的临床前研究中使用的血细胞来源于ES细胞在实验灵长类动物系统。(c)2006年国际实验血液学学会。爱思唯尔公司出版
Objective. Induction of hematopoietic cells from human embryonic stem (ES) cells has been reported recently. However, before cells derived from human ES cells can be used in the clinic, preclinical studies using these cells in experimental primates will be necessary. Therefore, we attempted to establish a method to induce hematopoietic cells robustly and abundantly from primate ES cells.Methods. A primate ES cell line, CMK-6, derived from the cynomolgus monkey was used in this study. We adapted a method to induce hematopoiesis from CMK-6 cells on feeder cells, and tested the effectiveness of three kinds of feeder cell lines (OP9, C2C12, and C3H10T1/2). In addition, we tested the effect of vascular endothelial growth factor (VEGF) and insulin-like growth factor-II (IGF-II) on hematopoiesis induction from CMK-6 cells.Results. VEGF and IGF-II showed an extremely strong synergistic effect to induce hematopoiesis from CMK-6 cells. C3H10T1/2 cells proved to be very useful for the induction of hematopoiesis from CMK-6 cells, and the production of blood cells on C3H10T1/2 cells has been maintained as long as 5 months. During this long period, ES cell derivatives continuously produced mature blood cells, including terminally differentiated cells.Conclusion. We have developed an original method to produce enriched blood cells abundantly from primate ES cells for an extremely long period. This method may represent a good in vitro model for studying primate hematopoiesis and related diseases. Furthermore, our method may be useful for preclinical studies of transfusion therapy using blood cells derived from ES cells in experimental primate systems. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc.