Revoltella R P, Papini S, Rosellini A, Michelini M
Institute of Biomedical Technologies, National Research Council of Italy, Pisa, Italy.
Cell Prolif. 2007 Aug;40(4):445-61. doi: 10.1111/j.1365-2184.2007.00450.x.
Epithelial stem cells of the eye surface, of the cornea and of the conjunctiva, have the ability to give rise to self renewal and progeny production of differentiated cells with no apparent limit. The two epithelia are separated from each other by the transition zone of the limbus. The mechanisms adopted by stem cells of the two epithelia to accomplish their different characteristics, and how their survival, replacement and unequal division that generates differentiated progeny formation are controlled, are complex and still poorly understood. They can be learned only by understanding how stem cells/progenitors are regulated by their neighbouring cells, that may themselves be differently unspecialised, forming particular microenvironments, known as 'niches'. Stem cells operate by signals and a variety of intercellular interactions and extracellular substrates with adjacent cells in the niche. Technical advances are now making it possible to identify zones in the corneal limbus and conjunctiva that can house stem cells, to isolate and expand them ex vivo and to control their behaviour creating optimal niche conditions. With improvements in biotechnology, regenerative cornea and conjunctiva transplantation using adult epithelial stem cells becomes now a reality.
Here we review our current understanding of stem cell niches and illustrate recent significant progress for identification and characterization of adult epithelial stem cells/progenitors at cellular, molecular and mechanistic levels, improvement in cell culture techniques for their selective expansion ex vivo and prospects for a variety of therapeutic applications.
眼表、角膜和结膜的上皮干细胞具有自我更新以及产生分化细胞后代的能力,且无明显限制。这两种上皮组织由角膜缘的过渡区彼此分隔。两种上皮组织的干细胞为实现其不同特性所采用的机制,以及它们的存活、替代和产生分化后代形成的不均等分裂是如何被控制的,这些都很复杂且仍知之甚少。只有通过了解干细胞/祖细胞如何受到其相邻细胞的调控才能知晓这些,而这些相邻细胞本身可能具有不同程度的未分化状态,从而形成特定的微环境,即“壁龛”。干细胞通过信号以及与壁龛中相邻细胞的多种细胞间相互作用和细胞外基质发挥作用。技术进步使得识别角膜缘和结膜中能够容纳干细胞的区域、在体外分离和扩增它们以及在创造最佳壁龛条件下控制其行为成为可能。随着生物技术的进步,使用成人上皮干细胞进行角膜和结膜再生移植现已成为现实。
在此,我们综述了目前对干细胞壁龛的理解,并阐述了在细胞、分子和机制层面识别和表征成人上皮干细胞/祖细胞方面的近期重大进展、体外选择性扩增它们的细胞培养技术的改进以及各种治疗应用的前景。