Niche regulation of limbal epithelial stem cells: HC-HA/PTX3 as surrogate matrix niche. (October 2020)

• Record Type: Journal Article
• Authors: Tseng, Scheffer C.G.; Chen, Szu-Yu; Mead, Olivia G.; Tighe, Sean
• Is Part Of: Experimental eye research. Volume 199(2020)
• Publication Date: 2020-10
• Subjects: Amniotic membrane -- HC-HA/PTX3 -- Limbus -- Limbal stem cell deficiency -- Niche -- Stem cell; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2020.108181
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: Homeostasis of the corneal epithelium is ultimately maintained by stem cells that reside in a specialized microenvironment within the corneal limbus termed palisades of Vogt. This limbal niche nourishes, protects, and regulates quiescence, self-renewal, and fate decision of limbal epithelial stem/progenitor cells (LEPCs) toward corneal epithelial differentiation. This review focuses on our current understanding of the mechanism by which limbal (stromal) niche cells (LNCs) regulate the aforementioned functions of LEPCs. Based on our discovery and characterization of a unique extracellular matrix termed HC-HA/PTX3 (Heavy chain (HC1)-hyaluronan (HA)/pentraxin 3 (PTX3) complex, "-" denotes covalent linkage; "/" denotes non-covalent binding) in the birth tissue, i.e., amniotic membrane and umbilical cord, we put forth a new paradigm that HC-HA/PTX3 serves as a surrogate matrix niche by maintaining the in vivo nuclear Pax6+ neural crest progenitor phenotype to support quiescence and self-renewal but prevent corneal fate decision of LEPCs. This new paradigm helps explain how limbal stem cell deficiency (LSCD) develops in aniridia due to Pax6-haplotype deficiency and further explains why transplantation of HC-HA/PTX3-containing amniotic membrane prevents LSCD in acute chemical burns and Stevens Johnson syndrome, augments the success of autologous LEPCs transplantation in patients suffering from partial or total LSCD, and assists ex vivo expansion (engineering) of a graft containing LEPCs. We thus envisage that this new paradigm based on regenerative matrix HC-HA/PTX3 as a surrogate niche can set a new standard for regenerative medicine in and beyond ophthalmology. Highlights: Salient features of limbal niche cells. HC-HA/PTX3 found in amniotic membrane and umbilical cord may serve as a surrogate matrix niche.for regenerative medicine in ophthalmology and beyond.