Risk factors for partial and total loss of limbal stem cells

Background: Endothelial Progenitor Cells (EPCs) are important players in neovascularization, mobilized through signalling by Angiogenic Growth Factors (AGFs) such as Vascular Endothelial Growth Factor (VEGF) and fibroblast growth factor (FGF). In vitro, inflammatory parameters impair the function and influence of EPCs on AGFs. However, this connection is not clear in vivo. To understand the mechanisms of augmented arteriogenesis and angiogenesis in acute ischemic stroke (AIS) patients, we investigated whether circulating stem cells (CD133+), early endothelial progenitor cells (CD133+/VEGFR2+), and endothelial cells (ECs; CD34¯/CD133¯/VEGFR2+) were increasingly mobilized during AIS, and whether there were correlations between EPC levels, growth factor levels and inflammatory parameters. Methods: Data on demographics, classical vascular risk factors, neurological deficit information (assessed using the National Institutes of Health Stroke Scale), and treatment were collected from 43 consecutive AIS patients (group I). Risk factor control patients (group II) included 22 nonstroke subjects matched by age, gender, and traditional vascular risk factors. EPCs were measured by flow cytometry and the populations of circulating stem cells (CD133+), early EPCs (CD133+/VEGFR2+), and ECs (CD34¯/CD133¯/VEGFR2+) were analysed. Correlations between EPC levels and VEGF and FGF vascular growth factor levels as well as the influence of inflammatory parameters on EPCs and AGFs were assessed. Results: Patient ages ranged from 54 to 92 years (mean age 75.2 ± 11.3 years). The number of circulating CD34¯/CD133¯/VEGF-R2+ cells was significantly higher in AIS patients than in control patients (p < 0.05). VEGF plasma levels were also significantly higher in AIS patients compared to control patients on day 7 (p < 0.05). FGF plasma levels in patients with AIS were significantly higher than those in the control group on day 3 (p < 0.05). There were no correlations between increased VEGF and FGF levels and the number of CD133+, CD133+/VEGFR2+, or CD34¯/CD133¯/VEGFR2+ cells. Leukocyte levels, FGF plasma levels, and the number of early EPCs were negatively correlated on day 3. High sensitivity C-reactive protein levels and the number of CD133+ and CD133+/VEGFR2+ cells were negatively correlated on day 7. In addition, there was a negative correlation between fibrinogen levels and FGF plasma levels as well as the number of early EPCs (CD133+/VEGFR2+). Conclusion: AIS patients exhibited increased numbers of early EPCs (CD133+/VEGFR2+) and AGF (VEGF and FGF) levels. A negative correlation between inflammatory parameters and AGFs and EPCs indicated the unfavourable influence of inflammatory factors on EPC differentiation and survival. Moreover, these correlations represented an important mechanism linking inflammation to vascular disease.

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Timolol induces necroptosis, apoptosis and senescence concentration-dependently in rabbit Limbal stem cells in vitro

Life Sciences ◽

10.1016/j.lfs.2021.119453 ◽

2021 ◽

pp. 119453

Author(s):

Guo-Jian Jiang ◽

Bei-Bei Li ◽

Ting-Jun Fan

Keyword(s):

Stem Cells ◽

Limbal Stem Cells

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Influence of height on endothelial maintenance activity: a narrative review

Environmental Health and Preventive Medicine ◽

10.1186/s12199-021-00941-5 ◽

2021 ◽

Vol 26 (1) ◽

Author(s):

Yuji Shimizu ◽

Takahiro Maeda

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Stem Cells ◽

Bone Marrow ◽

Hematopoietic Stem Cells ◽

Inverse Association ◽

Hematopoietic Stem ◽

Genetic Characteristics ◽

Maintenance Activity ◽

Marrow Activity

AbstractRecent studies have revealed an inverse association between height and cardiovascular disease. However, the background mechanism of this association has not yet been clarified. Height has also been reported to be positively associated with cancer. Therefore, well-known cardiovascular risk factors, such as increased oxidative stress and chronic inflammation, are not the best explanations for this inverse association because these risk factors are also related to cancer. However, impaired blood flow is the main pathological problem in cardiovascular disease, while glowing feeding vessels (angiogenesis) are the main characteristic of cancer pathologies. Therefore, endothelial maintenance activity, especially for the productivity of hematopoietic stem cells such as CD34-positive cells, could be associated with the height of an individual because this cell contributes not only to the progression of atherosclerosis but also to the development of angiogenesis. In addition, recent studies have also revealed a close connection between bone marrow activity and endothelial maintenance; bone marrow-derived hematopoietic stem cells contribute towards endothelial maintenance. Since the absolute volume of bone marrow is positively associated with height, height could influence endothelial maintenance activity. Based on these hypotheses, we performed several studies. The aim of this review is not only to discuss the association between height and bone marrow activity, but also to describe the potential mechanism underlying endothelial maintenance. In addition, this review also aims to explain some of the reasons that implicate hypertension as a major risk factor for stroke among the Japanese population. The review also aims to clarify the anthropological reasons behind the high risk of atherosclerosis progression in Japanese individuals with acquired genetic characteristics.

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Q-FIHC: Quantification of fluorescence immunohistochemistry to analysep63 isoforms and cell cycle phases in human limbal stem cells

Microscopy Research and Technique ◽

10.1002/jemt.20375 ◽

2006 ◽

Vol 69 (12) ◽

pp. 983-991 ◽

Cited By ~ 42

Author(s):

Enzo Di Iorio ◽

Vanessa Barbaro ◽

Stefano Ferrari ◽

Claudio Ortolani ◽

Michele De Luca ◽

...

Keyword(s):

Cell Cycle ◽

Stem Cells ◽

Limbal Stem Cells ◽

Cell Cycle Phases ◽

Fluorescence Immunohistochemistry

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STUDY ON EFFICACY OF CONJUNCTIVAL AUTOGRAFT SURGERY WITH LIMBAL STEM CELLS IN ADVANCED, RECURRENT PTERYGIUM

Journal of Evolution of Medical and Dental Sciences ◽

10.14260/jemds/2016/1397 ◽

2016 ◽

Vol 5 (83) ◽

pp. 6182-6185

Author(s):

Subbiah Vasan Chandrakumar ◽

Sudalaiyandi Ganapathirajesh ◽

Shanmugasami Kavitha ◽

Sundararajalu Abirami ◽

Mohanasundaram Vijayalakshmi ◽

...

Keyword(s):

Stem Cells ◽

Limbal Stem Cells ◽

Conjunctival Autograft ◽

Recurrent Pterygium

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Human Anterior Lens Capsule as a Biologic Substrate for the Ex Vivo Expansion of Limbal Stem Cells in Ocular Surface Reconstruction

Cornea ◽

10.1097/ico.0b013e318033bd0f ◽

2007 ◽

Vol 26 (4) ◽

pp. 473-478 ◽

Cited By ~ 40

Author(s):

Ahmed Galal ◽

Juan J Perez-Santonja ◽

Jose Luis Rodriguez-Prats ◽

Marta Abad ◽

Jorge Alio

Keyword(s):

Stem Cells ◽

Surface Reconstruction ◽

Ocular Surface ◽

Ex Vivo ◽

Ex Vivo Expansion ◽

Lens Capsule ◽

Limbal Stem Cells ◽

Ocular Surface Reconstruction ◽

Anterior Lens Capsule

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Cornea and Lens Problems in Aniridia

Aniridia and WAGR Syndrome ◽

10.1093/oso/9780195389302.003.0010 ◽

2010 ◽

Author(s):

Edward J. Holland ◽

Mayank Gupta

Keyword(s):

Stem Cells ◽

Epithelial Cells ◽

Corneal Epithelium ◽

Basal Layer ◽

Limbal Stem Cells ◽

Corneal Epithelial Cells ◽

Film Stability ◽

Corneal Epithelial ◽

Corneal Erosion ◽

Peripheral Cornea

The corneal epithelium is a rapidly regenerating, stratified squamous epithelium. Homeostasis of corneal epithelial cells is an important prerequisite, not only for the integrity of the ocular surface, but also for the visual function. The maintenance of a healthy corneal epithelium under both normal and wound-healing conditions is achieved by a population of stem cells located in the basal layer of limbal epithelium. The Limbus represents the transition zone between the peripheral cornea and the bulbar conjunctiva. The stem cells from the limbus generate the transient amplifying cells that migrate, proliferate, and differentiate to replace lost or damaged corneal epithelial cells. In patients with aniridia, there is a primary dysfunction of these limbal stem cells (see Figure 6.1). The cornea is affected clinically in 90 percent of the patients with aniridia. In most cases, the cornea in aniridic patients appears normal and transparent during infancy and childhood. However, during the early teens, the cornea begins to show changes. The early changes are marked by the in-growth of opaque epithelium from the limbal region into the peripheral cornea, which represents conjunctival epithelial cells, goblet cells, and blood vessels in the corneal epithelium. These changes gradually progress toward the central cornea and may cause corneal epithelial erosions and epithelial abnormalities that eventually culminate in opacification of the corneal stroma, which leads to vision loss. With the gradual loss of limbal stem cells, the entire cornea becomes covered with conjunctival cells. Eventually, many patients develop total limbal stem cell deficiency. These abnormalities usually become more pronounced with aging. The corneal abnormalities seen in aniridia are collectively termed “aniridic keratopathy”. Significant corneal opacification may occasionally be the initial manifestation of aniridia. Abnormal tear film stability and meibomian gland dysfunction are also observed in patients with aniridia. This can lead to dry eyes, aggravating corneal erosion and ulceration observed in aniridic patients. Sometimes, aniridia is associated with “Peter’s anomaly,” in which central corneal opacity is present at birth along with defects in the corneal endothelium and Descemet’s membrane.

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