Human limbal epithelial stem cell regulation, bioengineering and function. (November 2021) - Bonnet, Clémence
Abstract: The corneal epithelium is continuously renewed by limbal stem/progenitor cells (LSCs), a cell population harbored in a highly regulated niche located at the limbus. Dysfunction and/or loss of LSCs and their niche cause limbal stem cell deficiency (LSCD), a disease that is marked by invasion of conjunctival epithelium into the cornea and results in failure of epithelial wound healing. Corneal opacity, pain, loss of vision, and blindness are the consequences of LSCD. Successful treatment of LSCD depends on accurate diagnosis and staging of the disease and requires restoration of functional LSCs and their niche. This review highlights the major advances in the identification of potential LSC biomarkers and components of the LSC niche, understanding of LSC regulation, methods and regulatory standards in bioengineering of LSCs, and diagnosis and staging of LSCD. Overall, this review presents key points for researchers and clinicians alike to consider in deepening the understanding of LSC biology and improving LSCD therapies. Highlights: The limbal niche consists of unique cellular and molecular components. Wnt signaling pathways play a critical role in the survival and regulation of LSCs. Notch signaling regulates the differentiation and stratification of corneal epithelia. Xenobiotic-free cGMP LSC cultivation could raise the safety standards. Standardized LSCD diagnosis and staging criteria are necessary.