Lamba Deepak A, Karl Mike O, Ware Carol B, Reh Thomas A
Department of Biological Structure and Comparative Medicine, University of Washington, Seattle, WA 98195, USA.
Proc Natl Acad Sci U S A. 2006 Aug 22;103(34):12769-74. doi: 10.1073/pnas.0601990103. Epub 2006 Aug 14.
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.
视网膜易患退行性疾病,可导致失明。虽然在低等脊椎动物中视网膜再生能力很强,但成年哺乳动物的视网膜不会发生再生。因此,我们已经开发出了从人胚胎干细胞(hES细胞)中获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细胞系可被诱导成为视网膜祖细胞命运,并表达与源自人类胎儿视网膜的祖细胞相似的基因表达谱。hES细胞来源的祖细胞主要分化为具有功能性谷氨酸受体的视网膜内层神经元(神经节细胞和无长突细胞)。与源自视网膜变性小鼠模型的视网膜共培养时,hES细胞来源的视网膜祖细胞会与退化的小鼠视网膜整合,并增加其光感受器特异性标志物的表达。这些结果表明,人胚胎干细胞可以被选择性地诱导成为神经视网膜细胞命运,因此可能对治疗视网膜变性有用。