Regenerative Medicine - from Protocol to Patient by Gustav Steinhoff

Author:Gustav Steinhoff
Language: eng
Format: epub
Publisher: Springer International Publishing, Cham

The stem cells located at the limbal region play an important role in the normal maintenance of the corneal surface. The corneal epithelium is a highly dynamic structure and is constantly renewed all through the adulthood of an eye. The activated stem cells from the limbus migrate centripetally to the central cornea and helps in tissue homeostasis. As explained by XYZ theory (Thoft and Friend 1983) of corneal maintenance, the combined rate of cell proliferation and centripetal migration of the activated limbal stem cells (XY component) is equal to the rate of cell loss by desquamation (Z component).

Limbal epithelial stem cells (LESC) share common features with other adult somatic stem cells including small size (Bickenbach 1981; Holbrook and Odland 1975) and high nuclear to cytoplasmic ratio (Epstein et al. 2005). They also lack expression of differentiation markers such as cytokeratins 3 and 12 (Schermer et al. 1986; Fatima et al. 2006). LESCs are slow cycling during homeostasis and therefore retain DNA labels for long time periods, however in the event of corneal injury they can become highly proliferative (Park et al. 2006; Cotsarelis et al. 1989; Haskjold et al. 1989; Thompson et al. 1991) and contribute actively to healing of the wound. The basal epithelial stem cells located at the limbal niche express some of the markers such as, ∆Np63α (Pellegrini et al. 2001; Di Iorio et al. 2005), ABCG2 (Watanabe et al. 2004; Chen et al. 2004), C/EBPδ, Bmi1 (Barbaro et al. 2007), TCF4 (Lu et al. 2012), Frizzled 7 (Mei et al. 2014), ABCB5 (Ksander et al. 2014), SSEA4 (Mariappan et al 2014) and few others. These stem cells divide asymmetrically to maintain the reserve stem cell pool within the limbal niche. The limbal location of corneal epithelial stem cells provides a number of functional advantages. The basal cells of the cornea are devoid of any pigments and are highly susceptible to radiation induced damages. But the limbal region is pigmented and therefore the basal stem cells do not face this constraint. Also, the limbal epithelium has a highly undulating epithelial- stromal junctions and therefore are resistant to the shearing forces and provides maximum protection to the corneal stem cells (Van Buskirk 1989). It is important tot note that while the cornea is avascular, the limbal epithelium has a vascular bed which provides for the nourishment and maintenance of the limbal stem cells.

During wound healing process, the stem cells get activated and the transiently amplifying cells migrate in a centripetal manner which is a unique characteristic of the limbal epithelium. They undergo cell division and migrate centripetally towards the central cornea and also show a basal to upward movement towards the corneal surface. Once the epithelial cells leave the limbal basal layer or the limbal niche, they gradually activate the differentiation programme and differentiate into transiently amplifying cells (TAC) with lesser proliferative capacity and reduced stemness. Prior to or during the course of migration, these TAC become terminally differentiated and contribute to corneal wound healing by establishing cell-cell

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