Chondroitin Sulfate as a Potential Modulator of the Stem Cell Niche in Cornea

Abstract

Chondroitin sulfate (CS) is an important component of the extracellular matrix in multiple biological tissues. In cornea, the CS glycosaminoglycan (GAG) exists in hybrid form, whereby some of the repeating disaccharides are dermatan sulfate (DS). These CS/DS GAGs in cornea, through their presence on the proteoglycans, decorin and biglycan, help control collagen fibrillogenesis and organization. CS also acts as a regulatory ligand for a spectrum of signaling molecules, including morphogens, cytokines, chemokines, and enzymes during corneal growth and development. There is a growing body of evidence that precise expression of CS or CS/DS with specific sulfation motifs helps define the local extracellular compartment that contributes to maintenance of the stem cell phenotype. Indeed, recent evidence shows that CS sulfation motifs recognized by antibodies 4C3, 7D4, and 3B3 identify stem cell populations and their niches, along with activated progenitor cells and transitional areas of tissue development in the fetal human elbow. Various sulfation motifs identified by some CS antibodies are also specifically located in the limbal region at the edge of the mature cornea, which is widely accepted to represent the corneal epithelial stem cell niche. Emerging data also implicate developmental changes in the distribution of CS during corneal morphogenesis. This article will reflect upon the potential roles of CS and CS/DS in maintenance of the stem cell niche in cornea, and will contemplate the possible involvement of CS in the generation of eye-like tissues from human iPS (induced pluripotent stem) cells.

Photoinduced Gelatin-Methacrylate Scaffolds to Examine the Impact of Extracellular Environment on Trabecular Meshwork Cells

“…It has been previously reported that cultured hTM cells in the presence of Dex result in an enlargement of cells without change in proliferation. , Interestingly, human corneal keratocytes and corneal epithelial cell proliferation have been shown to be induced by low concentrations of Dex. , For the first week of study, the proliferation of cells on hydrogels containing GAGs, specifically CS, is higher, regardless of the presence or absence of Dex. This is most likely the result of the ability of CS to stimulate cell proliferation, as shown by previous research on TM and other cell types. − However, it remains unclear which biological pathway in the TM is impacted by exogenous CS leading to enhanced cell proliferation. After 2 weeks of culture, the presence of Dex did not impact cell proliferation within a hydrogel type except for GelMA/CS ones.…”

Commentary: Novel Cell Culture Paradigm Prolongs Mouse Corneal Epithelial Cell Proliferative Activity In Vitro and In Vivo

“…LSCs certainly need to communicate with their own niche to maintain self-renewal (Li et al, 2007), including specific extracellular matrix (ECM), niche cells, and signaling molecules (Ashworth et al, 2021). The ECM not only anchors the basal epithelium but also mediates intercellular communication and provides distinct mechanical properties that influence LSC phenotype, population, and self-renewal (Gesteira et al, 2017;Gouveia et al, 2019;Zheng et al, 2019;Zhu et al, 2020;Ashworth et al, 2021).…”

“…LSCs certainly need to communicate with their own niche to maintain self-renewal (Li et al, 2007), including specific extracellular matrix (ECM), niche cells, and signaling molecules (Ashworth et al, 2021). The ECM not only anchors the basal epithelium but also mediates intercellular communication and provides distinct mechanical properties that influence LSC phenotype, population, and self-renewal (Gesteira et al, 2017;Gouveia et al, 2019;Zheng et al, 2019;Zhu et al, 2020;Ashworth et al, 2021). Additionally, cell-cell communication analysis reveals the central role of LSCs and their bidirectional regulation with various niche cells, such as limbal-mesenchymal stem cells, CD45 + cells, PAX6 + cells, and melanocytes (Yazdanpanah et al, 2019;Altshuler et al, 2021;Chen et al, 2021;Polisetti et al, 2021).…”

Biofabrication of Artificial Stem Cell Niches in the Anterior Ocular Segment

“…Normally, in such cases, the neighbouring healthy endothelial cells spread out and change shape to cover the gaps left by lost cells, this is clinically known as polymegathism. However, a line of evidence has accumulated over recent years indicating that there is a putative population of endothelial progenitor cells (EPCs) that exhibit stem cell-like characteristics (expression of alkaline phosphatase and nestin) present in the peripheral endothelium (Table 4) [38,73,[90][91][92][93][94][95][96][97][98]. [95].…”