Limbal stem cell therapy.

Purpose Of Review: To highlight the progress and future direction of limbal stem cell (LSC) therapies for the treatment of limbal stem cell deficiency (LSCD).

Recent Findings: Direct LSC transplantation have demonstrated good long-term outcomes. Cultivated limbal epithelial transplantation (CLET) has been an alternative to treat severe to total LSCD aiming to improve the safety and efficacy of the LSC transplant.

Late-onset rupture of an intracranial dermoid cyst: a case report.

Background: Dermoid cysts are developmental abnormalities occurring between the third and fifth week of embryogenesis. These lesions can initially develop as intracranial or extracranial and persist throughout the patient's lifetime. While generally benign, their symptoms can be due to mass effect or local irritation secondary to rupture and release of contents, typically presenting as headaches and seizures.

Wnt activation as a potential therapeutic approach to treat partial limbal stem cell deficiency.

Limbal epithelial stem/progenitor cells (LSCs) are adult stem cells located at the limbus, tightly regulated by their niche involving numerous signaling pathways, such as Wnt. Wnt proteins are secreted morphogens that play critical roles in embryonic development, stem cell proliferation, self-renewal, tissue regeneration, and remodeling in adults. It has been shown that a small molecule Wnt mimic could improve LSCs expansion ex vivo.

Ocular Surface Regeneration by Limbal Stem Cells Therapies: State of the Art, Challenges, and Perspectives.

Limbal stem cells (LSCs) are adult stem cells located at the limbus ensuring the continuous renewal of the corneal epithelium, critical to maintain an optimal visual function. Damages to the LSCs or their niche microenvironment lead to limbal stem cell deficiency (LSCD), a potentially blinding disease. Transplantation of LSCs as a treatment for severe to total LSCD has gained popularity since 1980s, owing to the clinical success of the first direct limbal autograft transplantation.

Single mRNA detection of Wnt signaling pathway in the human limbus.

Limbal epithelial stem/progenitor cells (LSCs) are adult stem cells located at the limbus, tightly regulated by their close microenvironment. It has been shown that Wnt signaling pathway is crucial for LSCs regulation. Previous differential gene profiling studies confirmed the preferential expression of specific Wnt ligands (WNT2, WNT6, WNT11, WNT16) and Wnt inhibitors (DKK1, SFRP5, WIF1, FRZB) in the limbal region compared to the cornea.

Septic Arthritis With Superimposed Acute Gouty Arthritis in a Rheumatoid Arthritis Patient.

Septic arthritis is a rare but serious complication of both rheumatoid and gouty arthritis and can lead to significant morbidity and even mortality. Here, we report a case of septic arthritis with bacteremia, monosodium urate crystals, and hyperuricemia in a 75-year-old male with long-standing rheumatoid arthritis. Arthrocentesis revealed gram-positive cocci representing group B streptococcus () infection and monosodium urate crystals.

Partial Thrombosis of Inferior Mesenteric Vein With Thrombophlebitis.

Inferior mesenteric vein thrombosis (IMVT) is a rare entity that can lead to a potentially lethal event unless recognized early in the disease. Although its prevalence is low, IMVT presents mainly in certain conditions such as in inflammatory processes like diverticulitis, arrhythmias, hypercoagulable states, connective tissue disorders, malignancy, or hereditary thrombophilias.  Mesenteric venous thrombophlebitis is a condition in which a blood clot in a vein causes inflammation and pain.

The Role of Serial Imaging in Neurocysticercosis for Disease Resolution.

Neurocysticercosis (NCC), the most common parasitic infection of the CNS in humans, is a frequent cause of seizure disorders and epilepsy. The cystic larvae is endemic to developing countries where the population raises pigs as a reliable source of food, however, massive immigration has now forced the surge of the disease in developed areas making it a worldwide problem. Clinical presentation is affected by the size, number, and location of the lesions within the brain, with the most common manifestations being seizures, headaches, and increased intracranial pressure.

An Incidental Discovery Following Hypertension and Headaches: A Pheochromocytoma Case Report.

Pheochromocytomas (PCC) are rare neuroendocrine tumors of the adrenal medulla that arise from chromaffin cells. These cells are neural crest derivatives and are innervated by the splanchnic nerve of the sympathetic nervous system which releases acetylcholine that in turn binds to nicotinic acetylcholine receptors of the adrenal medulla causing the release of catecholamines. The dopamine, norepinephrine, and epinephrine released from these tumors are responsible for the episodic hyperadrenergic symptoms seen in these cases such as hypertension, palpitations, and headaches.

Human limbal epithelial stem cell regulation, bioengineering and function.

The corneal epithelium is continuously renewed by limbal stem/progenitor cells (LSCs), a cell population harbored in a highly regulated niche located at the limbus. Dysfunction and/or loss of LSCs and their niche cause limbal stem cell deficiency (LSCD), a disease that is marked by invasion of conjunctival epithelium into the cornea and results in failure of epithelial wound healing. Corneal opacity, pain, loss of vision, and blindness are the consequences of LSCD.

Expansion of Human Limbal Epithelial Stem/Progenitor Cells Using Different Human Sera: A Multivariate Statistical Analysis.

Transplantation of human cultured limbal epithelial stem/progenitor cells (LESCs) has demonstrated to restore the integrity and functionality of the corneal surface in about 76% of patients with limbal stem cell deficiency. However, there are different protocols for the expansion of LESCs, and many of them use xenogeneic products, being a risk for the patients' health. We compared the culture of limbal explants on the denuded amniotic membrane in the culture medium-supplemental hormone epithelial medium (SHEM)-supplemented with FBS or two differently produced human sera.

Role of Jagged1-mediated Notch Signaling Activation in the Differentiation and Stratification of the Human Limbal Epithelium.

The Notch signaling pathway plays a key role in proliferation and differentiation. We investigated the effect of Jagged 1 (Jag1)-mediated Notch signaling activation in the human limbal stem/progenitor cell (LSC) population and the stratification of the limbal epithelium in vitro. After Notch signaling activation, there was a reduction in the amount of the stem/progenitor cell population, epithelial stratification, and expression of proliferation markers.

mutant female mosquitoes show increased attraction to standing water.

The detection of water sources is crucial for insects such as mosquitoes to avoid desiccation and survive. In addition, mosquitoes use humidity cues to successfully navigate the environment to find a suitable oviposition site. Previous studies have implicated some members of the ionotropic receptor family in humidity sensing by .

Notch Inhibition Prevents Differentiation of Human Limbal Stem/Progenitor Cells in vitro.

Notch signaling has been shown to regulate the homeostasis and wound healing of the corneal epithelium. We investigated the effect of Notch inhibition in the human limbal stem/progenitor cells (LSCs) in vitro by using small molecules. Treatment of the LSCs with DAPT and SAHM1 reduced the proliferation rate and maintained the undifferentiated state of the LSCs in a concentration dependent manner.

Aedes aegypti Mosquitoes Detect Acidic Volatiles Found in Human Odor Using the IR8a Pathway.

Mosquitoes use olfaction as a primary means of detecting their hosts. Previously, the functional ablation of a family of Aedes aegypti olfactory receptors, the odorant receptors (ORs), was not sufficient to reduce host seeking in the presence of carbon dioxide (CO). This suggests the olfactory receptors that remain, such as the ionotropic receptors (IRs), could play a significant role in host detection.

Wnt Signaling Is Required for the Maintenance of Human Limbal Stem/Progenitor Cells In Vitro.

Purpose: A chemical approach to examine the role of Wnt signaling in maintaining the stemness and/or proliferation of limbal stem/progenitor cells (LSCs).

Methods: LSCs were isolated from human donor eyes and cultured as single cells for 12 to 14 days with the following small molecules: IIIC3, an antagonist of the Wnt signaling inhibitor Dickkopf (DKK), and IC15, a Wnt signaling inhibitor. Proliferation of LSCs in the presence of IIIC3 and IC15 was determined by the number of cells and colonies established.

Human adipose-derived stem cells support the growth of limbal stem/progenitor cells.

The most efficient method to expand limbal stem cells (LSCs) in vitro for clinical transplantation is to culture single LSCs directly on growth-arrested mouse fibroblast 3T3 cells. To reduce possible xenobiotic contamination from 3T3s, primary human adipose-derived stem cells (ASCs) were examined as feeder cells to support the expansion of LSCs in vitro. To optimize the ASC-supported culture, freshly isolated limbal epithelial cells in the form of single cells (SC-ASC) or cell clusters (CC-ASC) were cultured using three different methods: LSCs seeded directly on feeder cells, a 3-dimensional (3D) culture system and a 3D culture system with fibrin (fibrin 3D).

Comparative Study of Xenobiotic-Free Media for the Cultivation of Human Limbal Epithelial Stem/Progenitor Cells.

The culture of human limbal epithelial stem/progenitor cells (LSCs) in the presence of animal components poses the risk of cross-species contamination in clinical applications. We quantitatively compared different xenobiotic-free culture media for the cultivation of human LSCs. LSCs were cultured from 2 × 2 mm limbal tissue explants on denuded human amniotic membrane with different xenobiotic-free culture media: CnT-Prime (CnT-PR) supplemented with 0%, 1%, 5%, and 10% human serum (HS), embryonic stem cell medium (ESCM) alone or in combination with the standard supplemented hormonal epithelium medium (SHEM, control) at a 1:1 dilution ratio, and modified SHEM (mSHEM), in which cholera toxin and dimethyl sulfoxide (DMSO) were removed, isoproterenol was added, and the epidermal growth factor concentration was reduced.

Effect of Hypoxia-regulated Polo-like Kinase 3 (Plk3) on Human Limbal Stem Cell Differentiation.

Hypoxic conditions in the cornea affect epithelial function by activating Polo-like kinase 3 (Plk3) signaling and the c-Jun·AP-1 transcription complex, resulting in apoptosis of corneal epithelial cells. Hypoxic stress in the culture conditions also regulates limbal stem cell growth and fate. In this study, we demonstrate that there is a differential response of Plk3 in hypoxic stress-induced primary human limbal stem (HLS) and corneal epithelial (HCE) cells, resulting in different pathways of cell fate.

A 3D culture system enhances the ability of human bone marrow stromal cells to support the growth of limbal stem/progenitor cells.

The standard method of cultivating limbal epithelial progenitor/stem cells (LSCs) on a monolayer of mouse 3T3 feeder cells possesses the risk of cross-contamination in clinical applications. Human feeder cells have been used to eliminate this risk; however, efficiency from xenobiotic-free cultures on a monolayer appears to be lower than in the standard method using 3T3 cells. We investigated whether bone marrow stromal cells (BMSCs), also known as bone marrow-derived mesenchymal stem cells, could serve as feeder cells for the expansion of LSCs in the 3-dimensional (3D) system.

Ultrastructure of the posterior corneal stroma.

Purpose: To reinvestigate the ultrastructure of the posterior stroma of the human cornea and to correlate the findings with the stromal behavior after big-bubble creation.

Design: Observational consecutive 3-center case series.

Specimens: Fresh corneoscleral buttons from human donors (n = 19) and organ-cultured corneoscleral buttons (n = 10) obtained after Descemet's membrane endothelial keratoplasty.

Human limbal mesenchymal cells support the growth of human corneal epithelial stem/progenitor cells.

Purpose: We tested the viability of human limbal mesenchymal cells (LMCs) to support the expansion of human corneal epithelial stem/progenitor cells (LSCs).

Methods: Human LMCs were isolated from sclerocorneal tissue using collagenase A. Primary limbal epithelial cells (LECs) in the form of single cell suspension or cell clusters were cocultured on a monolayer of either 3T3 cells (control) or LMCs (SC-LMC culture).

A three-dimensional culture method to expand limbal stem/progenitor cells.

The current standard method to culture human limbal stem/progenitor cells (LSCs) in vitro is to culture limbal epithelial cells directly on a layer of murine 3T3 feeder cells (standard method). The direct contact between human cells and murine feeder cells poses the potential risk of incomplete removal of feeder cells after culture and cross-contamination in clinical applications. We present here a novel three-dimensional (3D) sandwich method in which LSCs and feeder cells were separately cultured on opposite sides of a porous membrane.

Presence of native limbal stromal cells increases the expansion efficiency of limbal stem/progenitor cells in culture.

Niche factors are important in the maintenance and regulation of stem cells. Limbal stromal cells are potentially a component of limbal stem cell (LSC) niche. We investigated the role of the limbal stromal cells in the ex vivo expansion of limbal stem/progenitor cells.

Extracellular Matrix is an Important Component of Limbal Stem Cell Niche.

Extracellular matrix plays an important role in stem cell niche which maintains the undifferentiated stem cell phenotype. Human corneal epithelial stem cells are presumed to reside mainly at the limbal basal epithelium. Efforts have been made to characterize different components of the extracellular matrix that are preferentially expressed at the limbus.