Photoreceptor loss causes irreversible blindness in many retinal diseases. The identification of suitable donor cell populations is of considerable interest because of their potential use to replace the photoreceptors lost in disease. Stem or progenitor cells that give rise to neurons and glia have been identified in several regions of the brain, including the embryonic retina and the ciliary epithelium of the adult eye, raising the possibility of autologous transplantation. However, there has been little systematic investigation into precisely which regions of the large mammalian adult eye give rise to such cells. Here, we show for the first time using the porcine eye the presence of progenitor cells in additional regions of the adult eye, including the pars plana and iris, regions that, in the human, are readily accessible during routine eye surgery. When cultured in the presence of growth factors, these cells proliferate to form neurospheres comprised of cells expressing retinal progenitor markers. Using an adherent monolayer culture system, these cells could be readily expanded to increase their number more than 1 million-fold and maintain a progenitor phenotype. When grown on the substrate laminin in the presence of serum, cells derived from both spheres and monolayer cultures differentiated into neurons and glia. These results suggest that a population of cells derived from the adult iris, pars plana, and ciliary body of a large mammalian species, the pig, has progenitor properties and neurogenic potential, thereby providing novel sources of donor cells for transplantation studies. Disclosure of potential conflicts of interest is found at the end of this article.

译文

:光感受器的丧失在许多视网膜疾病中导致不可逆转的失明。合适的供体细胞群体的鉴定具有相当大的兴趣,因为它们潜在地用于替代疾病中失去的感光细胞。在大脑的多个区域,包括成年眼的胚胎视网膜和睫状上皮,已经识别出产生神经元和神经胶质的干细胞或祖细胞,从而提高了自体移植的可能性。但是,很少有系统的研究来精确地确定成年哺乳动物大眼睛的哪些区域会产生这种细胞。在这里,我们首次使用猪眼显示了在成年眼的其他区域(包括平视和虹膜)中祖细胞的存在,这些区域在常规眼科手术中很容易进入人的区域。当在生长因子的存在下培养时,这些细胞增殖形成神经球,该神经球由表达视网膜祖细胞标记的细胞组成。使用贴壁单层培养系统,这些细胞可以轻松扩增,使其数量增加一百万倍以上,并保持祖细胞表型。当在血清存在下在层粘连蛋白上生长时,来自球体和单层培养物的细胞均分化为神经元和神经胶质细胞。这些结果表明,来源于大型哺乳动物物种的成年虹膜,平面和睫状体的细胞群具有祖细胞特性和神经源性潜力,从而为移植研究提供了新的供体细胞来源。在本文的末尾发现了潜在的利益冲突。

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