Wiley Interdiscip Rev Dev Biol. 2017 Nov 3. doi: 10.1002/wdev.303. [Epub ahead of print]

Limbal stem cells: identity, developmental origin, and therapeutic potential.

Gonzalez G^1,2, Sasamoto Y¹, Ksander BR³, Frank MH^4,5,6, Frank NY^1,2.

Abstract

The cornea is our window to the world and our vision is critically dependent on corneal clarity and integrity. Its epithelium represents one of the most rapidly regenerating mammalian tissues, undergoing full-turnover over the course of approximately 1-2 weeks. This robust and efficient regenerative capacity is dependent on the function of stem cells residing in the limbus, a structure marking the border between the cornea and the conjunctiva. Limbal stem cells (LSC) represent a quiescent cell population with proliferative capacity residing in the basal epithelial layer of the limbus within a cellular niche. In addition to LSC, this niche consists of various cell populations such as limbal stromal fibroblasts, melanocytes and immune cells as well as a basement membrane, all of which are essential for LSC maintenance and LSC-driven regeneration. The LSC niche's components are of diverse developmental origin, a fact that had, until recently, prevented precise identification of molecularly defined LSC. The recent success in prospective LSC isolation based on ABCB5 expression and the capacity of this LSC population for long-term corneal restoration following transplantation in preclinical in vivo models of LSC deficiency underline the considerable potential of pure LSC formulations for clinical therapy. Additional studies, including genetic lineage tracing of the developmental origin of LSC will further improve our understanding of this critical cell population and its niche, with important implications for regenerative medicine. For further resources related to this article, please visit the WIREs website.