The impact of age on the physical and cellular properties of the human limbal stem cell niche

Notara, Maria; Shortt, Alex J.; O’Callaghan, Anna R.; Daniels, Julie T.

doi:10.1007/s11357-011-9359-5

Cited by 64 publications

(65 citation statements)

References 44 publications

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“…However, the levels of putative stem cell markers and telomere length or telomerase activity do not show differences between ages [42]. Our results fit with these findings, as LSC from donors older than 60 years showed higher levels of the putative stem cell marker p63.…”

Section: Discussionsupporting

confidence: 89%

Limbal Stem Cells from Aged Donors Are a Suitable Source for Clinical Application

Nieto‐Nicolau

Martínez-Conesa

Casaroli‐Marano

2016

Stem Cells International

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Limbal stem cells (LSC) are the progenitor cells that maintain the transparency of the cornea. Limbal stem cell deficiency (LSCD) leads to corneal opacity, inflammation, scarring, and blindness. A clinical approach to treat this condition consists in LSC transplantation (LSCT) after ex vivo expansion of LSC. In unilateral LSCD, an autologous transplant is possible, but cases of bilateral LSCD require allogenic LSCT. Cadaveric donors represent the most important source of LSC allografts for treatment of bilateral LSCD when living relative donors are not available. To evaluate the suitability of aged cadaveric donors for LSCT, we compared three pools of LSC from donors of different ages (<60 years, 60–75 years, and >75 years). We evaluated graft quality in terms of percent of p63-positive (p63+) cells by immunofluorescence, colony forming efficiency, and mRNA and protein expression of p63, PAX6, Wnt7a, E-cadherin, and cytokeratin (CK) 12, CK3, and CK19. The results showed that LSC cultures from aged donors can express ≥3% of p63+ cells—considered as the minimum value for predicting favorable clinical outcomes after LSCT—suggesting that these cells could be a suitable source of LSC for transplantation. Our results also indicate the need to evaluate LSC graft quality criteria for each donor.

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Section: Discussionsupporting

confidence: 89%

Limbal Stem Cells from Aged Donors Are a Suitable Source for Clinical Application

Nieto‐Nicolau

Martínez-Conesa

Casaroli‐Marano

2016

Stem Cells International

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“…The influence of age on the niche topography has previously been described by Notara et al 20 Although the age range of the study population was narrow, we revealed an influence of age on the parameters for the right inferior (PD and Δ ERP ) and left superior (PD, Δ PR and Δ ERP ) limbal region. No influence was found for subject gender, although gender was not distributed equally.…”

Section: Discussionsupporting

confidence: 74%

A method for quantifying limbal stem cell niches using OCT imaging

et al. 2017

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AimsTo evaluate the efficacy of Fourier domain-optical coherence tomography (FD-OCT) in imaging and quantifying the limbal palisades of Vogt and to correlate these images with histological findings.MethodsThe superior and inferior limbal region of both eyes of 50 healthy volunteers were imaged by FD-OCT. Images were processed and analysed using Matlab software. In vitro immunofluorescent staining of a cadaveric donor limbus was analysed to correlate the presence of stem cells in the visualised structures.ResultsFD-OCT could successfully visualise limbal crypts and the palisades of Vogt in the limbus region. Fluorescent labelling confirmed the presence of stem cells in these structures. The mean palisade ridge width (ΔPR) and the mean interpalisade epithelial rete peg width (ΔERP) were both of the order of 72 μm, leading to a palisade density (PD) of about 7.4 palisades/mm. A significant difference in ΔPR, ΔERP and PD was seen between the inferior and superior sides of the right eye and the superior sides of the left and right eye(p<0.05.). A significant influence of iris colour on parameters ΔPR, ΔERP and PD was found, and of age on PD and ΔERP (p<0.05).ConclusionsIn vivo OCT imaging is a safe and effective modality to image the limbus and can be used to visualise the palisades of Vogt. Image processing using Matlab software enabled quantification and density calculation of imaged limbal palisades of Vogt. This technique may enhance targeted limbal biopsies for transplantation.

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“…After isolating epithelial cells for culture, as described previously, 18,19 the scleral and corneal part of the rims were cut off to leave approximately 1 mm on either side of the limbus. Subsequently, the tissue was dissected further into smaller fragments.…”

Section: Isolation and Culture Of Human Limbal Fibroblastsmentioning

confidence: 99%

“…As previously mentioned, it furthermore has been linked to effects of UV radiation. 18 While the main concern of most studies has been the assessment of the impact of UVB in the occurrence of pterygium, cataract, and skin tumors, the impact of UVA so far has been poorly studied. Epidemiologic studies have shown that the occurrence of pterygium was associated significantly with UVA and UVB.…”

mentioning

confidence: 99%

Short-Term Ultraviolet A Irradiation Leads to Dysfunction of the Limbal Niche Cells and an Antilymphangiogenic and Anti-inflammatory Micromilieu

Notara

Refaian

Braun

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. We analyzed the effects of short-term ultraviolet A (UVA) irradiation on the putative limbal stem cell phenotype, limbal fibroblasts, corneal inflammation, and corneal (lymph)angiogenic privilege.METHODS. Primary human limbal epithelial cells and fibroblasts were irradiated with 5.2 J/cm 2 of UVA. The limbal epithelial cell phenotype was assessed using P63a, cytokeratin 15, integrin b1 (marking stem and transient amplifying cells), and cytokeratin 3 (a differentiation marker) as well as by a colony-forming efficiency (CFE) assay. An epithelial-fibroblast coculture model was used to compare the ability of irradiated and nonirradiated fibroblasts to support the putative limbal stem cell phenotype. The effects of the conditioned media of irradiated and nonirradiated cells on proliferation and tube formation of human lymphatic and blood endothelial cells also were tested. The levels of factors related to angiogenesis and inflammation were assessed in a protein array and using ELISA.RESULTS. Ultraviolet A induced phenotypical changes of limbal epithelial cells, as their CFE and putative stem cell/transient amplifying marker expression decreased. Limbal epithelial cells cocultured with UVA-irradiated limbal fibroblasts also exhibited differentiation and CFE decrease. Conditioned media from irradiated limbal epithelial cells and fibroblasts inhibited lymphatic endothelial cell proliferation and tube network complexity. Levels of monocyte chemoattractant protein 1 (MCP1) were reduced following UVA irradiation of both cell populations, while levels of IFN-c increased in irradiated limbal epithelial cells.CONCLUSIONS. These data imply a key role of cellular components of the limbal niche following short-term UVA irradiation. Overall, UVA irradiation leads to dysfunction of these cells and a anti(lymph)angiogenic and anti-inflammatory micromilieu.

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The impact of age on the physical and cellular properties of the human limbal stem cell niche

Cited by 64 publications

References 44 publications

Limbal Stem Cells from Aged Donors Are a Suitable Source for Clinical Application

Limbal Stem Cells from Aged Donors Are a Suitable Source for Clinical Application

A method for quantifying limbal stem cell niches using OCT imaging

Short-Term Ultraviolet A Irradiation Leads to Dysfunction of the Limbal Niche Cells and an Antilymphangiogenic and Anti-inflammatory Micromilieu

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