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Advances and Perspectives in Limbal Epithelial Stem Cells and Their Niche

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 20 July 2025 | Viewed by 5336

Special Issue Editors

Dr. Naresh Polisetti

E-Mail Website
Guest Editor
Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Killianstrasse 5, 79106 Freiburg, Germany
Interests: limbal stem cell niche—cellular and molecular interactions; biomaterials—scaffolds for limbal epithelial stem cell expansion; limbal niche cells—biological role of limbal stem cell niche
Prof. Dr. Ursula Schlötzer-Schrehardt

E-Mail Website
Guest Editor
Department of Ophthalmology, University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, Germany
Interests: pathology and physiology of the limbal stem cell niche; limbal niche cell secretome and their biological role

Special Issue Information

Dear Colleagues,

The Special Issue, titled “Advances and Perspectives in Limbal Epithelial Stem Cells and Their Niche”, aims to provide a comprehensive overview of the most recent findings in the biology of limbal epithelial stem cells and their surrounding milieu. The interactions of limbal epithelial stem cells, the neural network that supports them, and other components such as immune cells, the extracellular matrix, and adjacent cells, primarily limbal mesenchymal stromal cells and melanocytes, maintain the homeostasis of limbal epithelial stem cells, which is pivotal for a healthy corneal surface. Limbal epithelial stem cells, limbal mesenchymal stromal cells, and limbal melanocytes have attracted increased attention in recent years due to their regenerative potential and implications for treating corneal diseases.

This Special Issue welcomes the submission of original research articles and reviews covering all aspects of limbal stem cell biology, including the signaling pathways that regulate their self-renewal and differentiation, the characterization of limbal stem cell markers, and their interactions with the surrounding microenvironment. Authors are encouraged to contribute novel insights into the molecular mechanisms underlying the behavior and function of limbal epithelial stem cells as well as the involvement of and the role of limbal niche cells in regulating limbal epithelial stem cell homeostasis.

In addition, this Special Issue also invites reviews and perspectives that summarize the current state of the field and identify future directions for research. These articles can provide valuable guidance for researchers who are interested in pursuing studies on limbal stem cells and their niche.

Overall, this Special Issue provides a platform for researchers to showcase their findings and contribute to the advancement of our understanding of the limbal stem cell niche microenvironment.

Dr. Naresh Polisetti
Prof. Dr. Ursula Schlötzer-Schrehardt
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • limbal epithelial stem cells
  • ocular surface
  • limbal stem cell niche
  • homeostasis
  • limbal mesenchymal stromal cells
  • regeneration
  • limbal melanocytes
  • extracellular matrix components

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Published Papers (3 papers)

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Research

18 pages, 2910 KiB  
Article
Anti-Inflammatory and Anti-(Lymph)angiogenic Properties of an ABCB5+ Limbal Mesenchymal Stem Cell Population
by Berbang Meshko, Thomas L. A. Volatier, Johanna Mann, Mark A. Kluth, Christoph Ganss, Markus H. Frank, Natasha Y. Frank, Bruce R. Ksander, Claus Cursiefen and Maria Notara
Int. J. Mol. Sci. 2024, 25(17), 9702; https://doi.org/10.3390/ijms25179702 - 7 Sep 2024
Viewed by 1729
Abstract
Corneal transparency and avascularity are essential for vision. The avascular cornea transitions into the vascularized conjunctiva at the limbus. Here, we explore a limbal stromal cell sub-population that expresses ABCB5 and has mesenchymal stem cell characteristics. Human primary corneal stromal cells were enriched [...] Read more.
Corneal transparency and avascularity are essential for vision. The avascular cornea transitions into the vascularized conjunctiva at the limbus. Here, we explore a limbal stromal cell sub-population that expresses ABCB5 and has mesenchymal stem cell characteristics. Human primary corneal stromal cells were enriched for ABCB5 by using FACS sorting. ABCB5+ cells expressed the MSC markers CD90, CD73, and CD105. ABCB5+ but not ABCB5− cells from the same donor displayed evidence of pluripotency with a significantly higher colony-forming efficiency and the ability of trilineage differentiation (osteogenic, adipogenic, and chondrogenic). The ABCB5+ cell secretome demonstrated lower levels of the pro-inflammatory protein MIF (macrophage migration inhibitory factor) as well as of the pro-(lymph)angiogenic growth factors VEGFA and VEGFC, which correlated with reduced proliferation of Jurkat cells co-cultured with ABCB5+ cells and decreased proliferation of blood and lymphatic endothelial cells cultured in ABCB5+ cell-conditioned media. These data support the hypothesis that ABCB5+ limbal stromal cells are a putative MSC population with potential anti-inflammatory and anti-(lymph)angiogenic effects. The therapeutic modulation of ABCB5+ limbal stromal cells may prevent cornea neovascularization and inflammation and, if transplanted to other sites in the body, provide similar protective properties to other tissues. Full article
(This article belongs to the Special Issue Advances and Perspectives in Limbal Epithelial Stem Cells and Their Niche)
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21 pages, 7418 KiB  
Article
Focal Adhesion Maturation Responsible for Behavioral Changes in Human Corneal Stromal Fibroblasts on Fibrillar Substrates
by Kirill E. Zhurenkov, Arseniy A. Lobov, Natalya B. Bildyug, Elga I. Alexander-Sinclair, Diana M. Darvish, Ekaterina V. Lomert, Daria V. Kriger, Bozhana R. Zainullina, Alina S. Chabina, Julia I. Khorolskaya, Daria A. Perepletchikova, Miralda I. Blinova and Natalia A. Mikhailova
Int. J. Mol. Sci. 2024, 25(16), 8601; https://doi.org/10.3390/ijms25168601 - 7 Aug 2024
Viewed by 1180
Abstract
The functioning of the human cornea heavily relies on the maintenance of its extracellular matrix (ECM) mechanical properties. Within this context, corneal stromal fibroblasts (CSFs) are essential, as they are responsible for remodeling the corneal ECM. In this study, we used a decellularized [...] Read more.
The functioning of the human cornea heavily relies on the maintenance of its extracellular matrix (ECM) mechanical properties. Within this context, corneal stromal fibroblasts (CSFs) are essential, as they are responsible for remodeling the corneal ECM. In this study, we used a decellularized human amniotic membrane (dHAM) and a custom fibrillar collagen film (FCF) to explore the effects of fibrillar materials on human CSFs. Our findings indicate that substrates like FCF can enhance the early development of focal adhesions (FAs), leading to the activation and propagation of mechanotransduction signals. This is primarily achieved through FAK autophosphorylation and YAP1 nuclear translocation pathways. Remarkably, inhibiting FAK autophosphorylation negated the observed changes. Proteome analysis further confirmed the central role of FAs in mechanotransduction propagation in CSFs cultured on FCF. This analysis also highlighted complex signaling pathways, including chromatin epigenetic modifications, in response to fibrillar substrates. Overall, our research highlights the potential pathways through which CSFs undergo behavioral changes when exposed to fibrillar substrates, identifying FAs as essential mechanotransducers. Full article
(This article belongs to the Special Issue Advances and Perspectives in Limbal Epithelial Stem Cells and Their Niche)
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18 pages, 12979 KiB  
Article
Influence of Organ Culture on the Characteristics of the Human Limbal Stem Cell Niche
by Naresh Polisetti, Gottfried Martin, Eva Ulrich, Mateusz Glegola, Ursula Schlötzer-Schrehardt, Günther Schlunck and Thomas Reinhard
Int. J. Mol. Sci. 2023, 24(23), 16856; https://doi.org/10.3390/ijms242316856 - 28 Nov 2023
Cited by 7 | Viewed by 1592
Abstract
Organ culture storage techniques for corneoscleral limbal (CSL) tissue have improved the quality of corneas for transplantation and allow for longer storage times. Cultured limbal tissue has been used for stem cell transplantation to treat limbal stem cell deficiency (LSCD) as well as [...] Read more.
Organ culture storage techniques for corneoscleral limbal (CSL) tissue have improved the quality of corneas for transplantation and allow for longer storage times. Cultured limbal tissue has been used for stem cell transplantation to treat limbal stem cell deficiency (LSCD) as well as for research purposes to assess homeostasis mechanisms in the limbal stem cell niche. However, the effects of organ culture storage conditions on the quality of limbal niche components are less well described. Therefore, in this study, the morphological and immunohistochemical characteristics of organ-cultured limbal tissue are investigated and compared to fresh limbal tissues by means of light and electron microscopy. Organ-cultured limbal tissues showed signs of deterioration, such as edema, less pronounced basement membranes, and loss of the most superficial layers of the epithelium. In comparison to the fresh limbal epithelium, organ-cultured limbal epithelium showed signs of ongoing proliferative activity (more Ki-67+ cells) and exhibited an altered limbal epithelial phenotype with a loss of N-cadherin and desmoglein expression as well as a lack of precise staining patterns for cytokeratin ((CK)14, CK17/19, CK15). The analyzed extracellular matrix composition was mainly intact (collagen IV, fibronectin, laminin chains) except for Tenascin-C, whose expression was increased in organ-cultured limbal tissue. Nonetheless, the expression patterns of cell–matrix adhesion proteins varied in organ-cultured limbal tissue compared to fresh limbal tissue. A decrease in the number of melanocytes (Melan-A+ cells) and Langerhans cells (HLA-DR+, CD1a+, CD18+) was observed in the organ-cultured limbal tissue. The organ culture-induced alterations of the limbal epithelial stem cell niche might hamper its use in the treatment of LSCD as well as in research studies. In contrast, reduced numbers of donor-derived Langerhans cells seem associated with better clinical outcomes. However, there is a need to consider the preferential use of fresh CSL for limbal transplants and to look at ways of improving the limbal stem cell properties of stored CSL tissue. Full article
(This article belongs to the Special Issue Advances and Perspectives in Limbal Epithelial Stem Cells and Their Niche)
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