Evaluating alternative stem cell hypotheses for adult corneal epithelial maintenance.
Evaluating alternative stem cell hypotheses for adult corneal epithelial maintenance.
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DOI：
10.4252/wjsc.v7.i2.281
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发表时间：
2015-03
影响因子：
4.1
通讯作者：
J. West;Natalie J. Dorà;J. Collinson
中科院分区：
文献类型：
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作者：
J. West;Natalie J. Dorà;J. Collinson
在这篇综述中，我们评估了三种不同的假设，解释如何维持角膜上皮的证据。角膜缘上皮干细胞（LESC）假说是最广泛接受的。这表明，角膜缘上皮基底层中的干细胞，在角膜的周边，保持自己，也产生瞬时（或过境）放大细胞（TAC）。然后，TAC向心性移动到角膜上皮基底层中的角膜中心，并且还补充上覆基底层中的细胞。LESC在正常稳态期间维持角膜上皮，并且变得更活跃以修复显著伤口。其次，角膜上皮干细胞（CESC）假说假设，在正常的稳态，干细胞分布在整个基底角膜上皮，维持组织。根据这一假设，LESC存在于利姆布斯中，但仅在伤口愈合期间有活性。我们还考虑了第三种可能性，即角膜上皮在正常稳态期间通过基底角膜上皮细胞的增殖来维持，而没有来自干细胞的任何输入。在回顾了已发表的证据后，我们得出结论，LESC和CESC假设与第三种假设相比，与更多的证据相一致，因此我们不进一步考虑这一点。LESC和CESC假设都难以解释一种主要类型的证据，因此我们评估了区分它们的两条关键证据线。最后，我们将讨论如何血统追踪实验已经开始解决的争论，有利于LESC假说。然而，如果角膜缘干细胞功能受损，一些基底角膜上皮细胞也可能作为长期祖细胞。因此，这方面的CESC假说可能有一个持久的影响，我们对角膜上皮维护的理解，即使它最终表明，干细胞仅限于利姆布斯提出的LESC假说。
In this review we evaluate evidence for three different hypotheses that explain how the corneal epithelium is maintained. The limbal epithelial stem cell (LESC) hypothesis is most widely accepted. This proposes that stem cells in the basal layer of the limbal epithelium, at the periphery of the cornea, maintain themselves and also produce transient (or transit) amplifying cells (TACs). TACs then move centripetally to the centre of the cornea in the basal layer of the corneal epithelium and also replenish cells in the overlying suprabasal layers. The LESCs maintain the corneal epithelium during normal homeostasis and become more active to repair significant wounds. Second, the corneal epithelial stem cell (CESC) hypothesis postulates that, during normal homeostasis, stem cells distributed throughout the basal corneal epithelium, maintain the tissue. According to this hypothesis, LESCs are present in the limbus but are only active during wound healing. We also consider a third possibility, that the corneal epithelium is maintained during normal homeostasis by proliferation of basal corneal epithelial cells without any input from stem cells. After reviewing the published evidence, we conclude that the LESC and CESC hypotheses are consistent with more of the evidence than the third hypothesis, so we do not consider this further. The LESC and CESC hypotheses each have difficulty accounting for one main type of evidence so we evaluate the two key lines of evidence that discriminate between them. Finally, we discuss how lineage-tracing experiments have begun to resolve the debate in favour of the LESC hypothesis. Nevertheless, it also seems likely that some basal corneal epithelial cells can act as long-term progenitors if limbal stem cell function is compromised. Thus, this aspect of the CESC hypothesis may have a lasting impact on our understanding of corneal epithelial maintenance, even if it is eventually shown that stem cells are restricted to the limbus as proposed by the LESC hypothesis.