Efficient generation of retinal progenitor cells from human embryonic stem cells
Efficient generation of retinal progenitor cells from human embryonic stem cells
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DOI：
10.1073/pnas.0601990103
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发表时间：
2006-08-22
影响因子：
11.1
通讯作者：
Reh, Thomas A.
中科院分区：
文献类型：
--
作者：
Lamba, Deepak A.;Karl, Mike O.;Reh, Thomas A.
视网膜容易退化，导致失明。虽然视网膜再生在低等脊椎动物中是强健的，但在成年哺乳动物视网膜中不会发生再生。因此，我们已经开发了从人胚胎干细胞（hES）中提取视网膜神经元的有效方法。在适当的培养条件下，高达80%的H1系可以定向到视网膜祖细胞的命运，并表达类似于来自人类胎儿视网膜的祖细胞的基因表达谱。hES细胞衍生的祖细胞主要分化为视网膜内神经元（神经节细胞和无突细胞），具有功能性谷氨酸受体。在与小鼠视网膜变性模型视网膜共培养后，hES细胞衍生的视网膜祖细胞与退化的小鼠视网膜整合，并增加其光受体特异性标记物的表达。这些结果表明，人类胚胎干细胞可以选择性地定向到神经视网膜细胞的命运，因此可能在视网膜变性的治疗中有用。
The retina is subject to degenerative conditions, leading to blindness. Although retinal regeneration is robust in lower vertebrates, regeneration does not occur in the adult mammalian retina. Thus, we have developed efficient methods for deriving retinal neurons from human embryonic stem (hES) cells. Under appropriate culture conditions, up to 80% of the H1 line can be directed to the retinal progenitor fate, and express a gene expression profile similar to progenitors derived from human fetal retina. The hES cell-derived progenitors differentiate primarily into inner retinal neurons (ganglion and amacrine cells), with functional glutamate receptors. Upon coculture with retinas derived from a mouse model of retinal degeneration, the hES cell derived retinal progenitors integrate with the degenerated mouse retina and increase in their expression of photoreceptor-specific markers. These results demonstrate that human ES cells can be selectively directed to a neural retinal cell fate and thus may be useful in the treatment of retinal degenerations.