Advanced Imaging and Tissue Engineering of the Human Limbal Epithelial Stem Cell Niche

Massie, Isobel; Dziasko, Marc; Kureshi, Alvena; Levis, Hannah J.; Morgan, Louise; Neale, Michael H.; Sheth, Radhika; Tovell, Victoria E.; Vernon, Amanda; Funderburgh, James L.; Daniels, Julie T.

doi:10.1007/978-1-4939-1785-3_15

Cited by 21 publications

(23 citation statements)

References 10 publications

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“…One very important aspect for obtaining nanoscale structural and chemical information to be able to study the breakdown and processing of MNPs, of course, is the preparation and conditioning of tissue materials which precedes all of the advanced imaging and analysis techniques. We refer here to previous works that give excellent overviews of the tissue preparation techniques [49, 55, 74]. …”

Section: The Role Of Cellular Breakdown and In Vivo Processing Of Nanmentioning

confidence: 99%

From Dose to Response: In Vivo Nanoparticle Processing and Potential Toxicity

Graham

Jacobs

Yokel

et al. 2017

Advances in Experimental Medicine and Biology

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Adverse human health impacts due to occupational and environmental exposures to manufactured nanoparticles are of concern and pose a potential threat to the continued industrial use and integration of nanomaterials into commercial products. This chapter addresses the inter-relationship between dose and response and will elucidate on how the dynamic chemical and physical transformation and breakdown of the nanoparticles at the cellular and subcellular levels can lead to the in vivo formation of new reaction products. The dose-response relationship is complicated by the continuous physicochemical transformations in the nanoparticles induced by the dynamics of the biological system, where dose, bio-processing, and response are related in a non-linear manner. Nanoscale alterations are monitored using high-resolution imaging combined with in situ elemental analysis and emphasis is placed on the importance of the precision of characterization. The result is an in-depth understanding of the starting particles, the particle transformation in a biological environment, and the physiological response.

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Section: The Role Of Cellular Breakdown and In Vivo Processing Of Nanmentioning

confidence: 99%

From Dose to Response: In Vivo Nanoparticle Processing and Potential Toxicity

Graham

Jacobs

Yokel

et al. 2017

Advances in Experimental Medicine and Biology

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“…The limbal niche within the PV consists of the (a) cellular elements such as immune cells, mesenchymal cells, melanocytes, vascular and nerve cells; (b) extracellular matrix (ECM); and (c) signaling molecules [7, 8, 22, 23]. Precise and coordinated function of all the components of limbal niche is crucial for appropriate proliferation, migration and differentiation of LESCs.…”

Section: Limbus Limbal Niche and Limbal Homeostasismentioning

confidence: 99%

“…The limbal niche has been examined in-depth using advanced imaging, cellular and molecular analyses [22, 25•, 26, 27••]. Anatomically, the PVs correspond to projections of stroma into basal epithelial layer (Fig.…”

Section: Limbus Limbal Niche and Limbal Homeostasismentioning

confidence: 99%

“…Therefore, as explained above, limbal niche deficiency/dysfunction plays a major pathologic role in the loss of the regenerative capacity of the LESCs. With further developments in imaging technologies, it is expected that examination of the limbal niche will become a standard part of the diagnosis of LESC disorders in the near future [6, 22]. …”

Section: Pathological Alterations Of the Limbal Nichementioning

confidence: 99%

“…Creation of a whole limbal niche is under investigation by tissue engineering approaches [22]. Applying anti-inflammatory tissues like amniotic membrane and its derivatives [9•], blood-derived products [57], and growth factors [58] have revealed significant results in experimental studies.…”

Section: Therapeutic Approaches: Restoring the Limbal Niche As A Prommentioning

confidence: 99%

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Limbal and corneal epithelial homeostasis

Yazdanpanah

Jabbehdari²,

Djalilian

2017

Current Opinion in Ophthalmology

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Purpose of Review The aim of this review is to describe the underlying mechanisms of corneal epithelial homeostasis in addition to illustrating the vital role of the limbal epithelial stem cells (LESCs) and the limbal niche in epithelial regeneration and wound healing. Recent Findings The shedded corneal epithelial cells are constantly replenished by the LESCs which give rise to epithelial cells that proliferate, differentiate and migrate centripetally. While some recent studies have proposed that epithelial stem cells may also be present in the central cornea, the predominant location for the stem cells is the limbus. The limbal niche is the specialized micro-environment consisting of cells, extra-cellular matrix and signaling molecules that are essential for the function of LESCs. Disturbances to limbal niche can result in LESC dysfunction, therefore, limbal stem cell deficiency should also be considered a limbal niche deficiency. Current and in–development therapeutic strategies are aimed at restoring the limbal niche, by medical and/or surgical treatments, administration of trophic factors and cell based therapies. Summary The corneal epithelium is constantly replenished by LESCs that are housed within the limbal niche. The limbal niche is the primary determinant of the LESC function and novel therapeutic approaches should be focused on regeneration of this microenvironment.

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Cell Adhesion Molecules and Stem Cell-Niche-Interactions in the Limbal Stem Cell Niche

et al. 2015

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Interactions between stem cells and their microenvironment are critical for regulation and maintenance of stem cell function. To elucidate the molecular interactions within the human limbal epithelial stem/progenitor cell (LEPC) niche, which is essential for maintaining corneal transparency and vision, we performed a comprehensive expression analysis of cell adhesion molecules (CAMs) using custom-made quantitative real-time polymerase chain reaction (qRT-PCR) arrays and laser capture-microdissected LEPC clusters, comprising LEPCs, melanocytes, mesenchymal cells, and transmigrating immune cells. We show that LEPCs are anchored to their supporting basement membrane by the laminin receptors a3b1 and a6b4 integrin and the dystroglycan complex, while intercellular contacts between LEPCs and melanocytes are mediated by N-, P-, and E-cadherin together with L1-CAM, a member of the immunoglobulin superfamily (Ig)CAMs. In addition to the LEPC-associated heparan sulfate proteoglycans syndecan-2, glypican-3, and glypican-4, the IgCAM members ICAM-1 and VCAM-1 were found to be variably expressed on LEPCs and associated niche cells and to be dynamically regulated in response to chemokines such as interferon-c to enhance interactions with immune cells. Moreover, junctional adhesion molecule JAM-C accumulating in the subepithelial limbal matrix, appeared to be involved in recruitment of immune cells, while mesenchymal stromal cells appeared to use the nephronectin receptor integrin a8 for approaching the limbal basement membrane. In summary, we identified a novel combination of cell surface receptors that may regulate both stable and dynamic cell-matrix and cell-cell interactions within the limbal niche. The findings provide a solid foundation for further functional studies and for advancement of our current therapeutic strategies for ocular surface reconstruction. STEM CELLS 2016;34:203-219 SIGNIFICANCE STATEMENTThe study provides novel data on the molecular composition of the human limbal stem cell niche by identification of a combination of cell surface receptors that regulate both stable and dynamic cell-matrix and cell-cell interactions within the limbal niche. Most of the molecules identified, i.e. dystroglycan-1, integrin a8, nephronectin, syndecan-2, glypicans-3 and -4, L1-CAM, and JAM-C, have not been described before in the context of the limbal niche. In addition, the ICAM-1/ VCAM-1-mediated interaction of limbal epithelial progenitor cells with immune cells, which could be regulated by chemokines such as interferon-c, provides a novel view of the dynamic nature of the limbal niche. Moreover, we demonstrated the usability of surface molecules such as L1-CAM for isolation and enrichment of limbal progenitor and niche cells.Although being still on a rather descriptive level, the findings provide insights into molecular mechanisms of progenitor cell-niche anchorage mediated by integrins, cadherins, and dystrophin-associated proteins, and into dynamic physical interactions with immune cells mediated by immunoglob...

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Advanced Imaging and Tissue Engineering of the Human Limbal Epithelial Stem Cell Niche

Cited by 21 publications

References 10 publications

From Dose to Response: In Vivo Nanoparticle Processing and Potential Toxicity

From Dose to Response: In Vivo Nanoparticle Processing and Potential Toxicity

Limbal and corneal epithelial homeostasis

Cell Adhesion Molecules and Stem Cell-Niche-Interactions in the Limbal Stem Cell Niche

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