Fetal hepatic progenitors support long-term expansion of hematopoietic stem cells.

Fetal hepatic progenitors support long-term expansion of hematopoietic stem cells.
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DOI:
10.1016/j.exphem.2013.02.003
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发表时间:
2013-05
影响因子:
2.6
通讯作者:
Lodish, Harvey F.
Lodish, Harvey F.
中科院分区:
医学4区
文献类型:
--
作者:
Chou, Song;Flygare, Johan;Lodish, Harvey F.

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我们已经开发了一种共培养系统,该系统将DLK+胎肝祖细胞建立为用于扩增造血干细胞(HSC)和祖细胞的真实支持细胞。在补充有血清和支持性细胞因子的1周培养物中,共培养的DLK+胎肝祖细胞及其条件培养基均支持造血祖细胞的快速扩增和HSC数量的小幅增加。在2周和3周的培养物中,DLK+细胞,而不是它们的条件培养基,连续且显著地(>20倍)扩增造血干细胞和祖细胞。HSC和DLK+细胞之间的物理接触对于维持这种长期扩增至关重要。在使用无血清、低精氨酸含量培养基的共培养物中实现了类似的HSC扩增(约7倍)。相反,DLK−细胞不能扩增造血细胞,这表明肝祖细胞是胎肝中HSC扩增的主要支持细胞。
We have developed a coculture system that establishes DLK+ fetal hepatic progenitors as the authentic supportive cells for expansion of hematopoietic stem (HSCs) and progenitor cells. In 1-week cultures supplemented with serum and supportive cytokines, both cocultured DLK+ fetal hepatic progenitors and their conditioned medium supported rapid expansion of hematopoietic progenitors and a small increase in HSC numbers. In 2- and 3-week cultures DLK+ cells, but not their conditioned medium, continuously and significantly (>20-fold) expanded both hematopoietic stem and progenitor cells. Physical contact between HSCs and DLK+ cells was crucial to maintaining this long-term expansion. Similar HSC expansion (approximately sevenfold) was achieved in cocultures using a serum-free, low cytokine-containing medium. In contrast, DLK− cells are incapable of expanding hematopoietic cells, demonstrating that hepatic progenitors are the principle supportive cells for HSC expansion in the fetal liver.
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