Agate Noer

• PhD
• Oslo University Hospital

Introduction: This report presents a case of an exceptionally delayed distant recurrence of a choroidal melanoma, occurring 4 decades after the enucleation of the affected eye. Case Presentation: In 1977, a 29-year-old man underwent enucleation for a choroidal melanoma. At the age of 68 years, he was diagnosed with advanced prostate cancer. Althoug...

Aims/Purpose: Identify the distribution of the most commonly used markers for stemness, quiescence, proliferation, and differentiation in limbal compartments such as human limbal epithelial crypts, posterior and anterior limbus, as well as the central and posterior cornea . Methods: Corneal‐limbal biopsies from cadaver human donors ( n = 3) embedde...

Human limbal epithelial stem cells (hLESCs) continuously replenish lost or damaged human corneal epithelial cells. The percentage of stem/progenitor cells in autologous ex vivo expanded tissue is essential for the long-term success of transplantation in patients with limbal epithelial stem cell deficiency. However, the molecular processes governing...

We aimed to investigate whether a novel technique of human amniotic membrane (HAM) preparation that mimics the crypts in the limbus enhances the number of progenitor cells cultured ex vivo. The HAMs were sutured on polyester membrane (1) standardly, to obtain a flat HAM surface, or (2) loosely, achieving the radial folding to mimic crypts in the li...

Purpose: Human limbal epithelial stem cells (HLESCs) reside in limbal epithelial crypts and continuously compensate for the loss of cells in the corneal epithelium. The lack or malfunction of HLESCs leads to a severe ocular surface disease called limbal epithelial stem cell deficiency (LSCD). Cultivated limbal epithelial stem cell transplantation (...

Purpose Uveal melanoma (UM) is an aggressive malignancy, in which nearly 50% of the patients die from metastatic disease. Aberrant DNA methylation is recognized as an important epigenomic event in carcinogenesis. Formalin-fixed paraffin-embedded (FFPE) samples represent a valuable source of tumor tissue, and recent technology has enabled the use of...

Late spontaneous in-the-bag intraocular lens (IOL) dislocation is a complication presenting 6 months or later after cataract surgery. We aimed to characterize the cells in the lens capsules (LCs) of 18 patients with spontaneous late in-the-bag IOL dislocation. Patients' average age was 82.6 ± 1.5 years (range 72–98), and most of them had pseudoexfo...

Materials and methods: Proliferative cells were isolated from the peripheral retina of human eyes (n = 6) within 24 to 48 hours post mortem and further expanded for 2 or 3 passages before being differentiated for 1-3 weeks. Gene expression was analyzed by microarray and qRT-PCR analysis, while protein expression was identified by immunocytochemist...

Purpose Uveal melanoma (UM) has a high propensity for metastatic spread, and approximately 40–50% of patients die of metastatic disease. Metastases can be found at the time of diagnosis but also several years after the tumor has been removed. The survival of disseminated cancer cells is known to be linked to anchorage independence, anoikis resistan...

Introduction: Multilamellar bodies (MLBs) are concentric cytoplasmic membranes which form through an autophagy-dependent mechanism. In the cornea, the presence of MLBs is associated with Schnyder corneal dystrophy (SCD). Ex vivo 3D modelling of the corneal stroma and SCD can help study pathogenesis and resolution of the disorder. Methods: Cornea...

Purpose Limbal stem cell deficiency, secondary to insults and diseases, may be treated by transplantation of ex vivo engineered epithelial grafts. We here present preliminary data on levels of cellular DNA damage in grafts produced in two different types of culture medium. Methods Cultures were initiated using corneo-limbal donor tissue after remo...

Purpose To examine the effect of medium and substrate on morphology, on expression of selected keratins and on global gene expression in ex vivo engineered corneo-limbal grafts. Methods Limbal biopsies retrieved from corneo-scleral rings of cadaveric donors were placed on human amniotic membranes or on plastic inserts and cultured for 3 weeks in p...

Purpose To examine correlation of DNA methylation patterns of human uveal melanoma with survival. Methods FFPE samples from 24 UM patients undergoing enucleation of the eye in the period 1976–1989 were included. Inclusion was based on histopathological data, data from the Norwegian Cancer Registry and the Norwegian Cause of Death Registry. DNA was...

Patients with limbal stem cell deficiency (LSCD) often experience pain and photophobia due to recurrent epithelial defects and chronic inflammation of the cornea. Successfully restoring a healthy corneal surface in these patients by transplantation of ex vivo expanded human limbal epithelial cells (LECs) may alleviate these symptoms and significant...

Purpose Biocompatible and bioactive substrates are important in tissue engineering. The nature of these substrates can directly influence cellular response, ultimately affecting the rate and quality of new tissue formation. A novel atomic layer deposition/molecular layer deposition (ALD/MLD) technique was used to build cell culture substrates to do...

Purpose Electrospun polymer nanofibers present a structure similar to extracellular matrix (ECM) and support the surrounding cells. The type of polymer used, as well as the polymer blending-ratio, affects wettability. This in turn influences cell growth by altering the types of proteins adsorbed from the solution. Human corneal epithelial cells wer...

Long-term cultures of cornea limbal epithelial stem cells (LESCs) were developed and characterized for future tissue engineering and clinical applications. The limbal tissue explants were cultivated and expanded for more than 3 months in medium containing serum as the only growth supplement and without use of scaffolds. Viable 3D cell outgrowth fro...

Purpose Uveal melanoma ( UM ) is the most common intraocular malignancy and is fatal in approximately 50% of the cases. Cancer relapse can be seen years after treatment. Diverse mechanisms have been proposed to explain the late relapse of UM e.g cancer dormancy and the presence of cancers stem cells ( CSC s). UM has the disadvantage of being diffic...

Limbal stem cell deficiency, secondary to insults and diseases, may be treated by transplantation of ex vivo engineered epithelial grafts. We here present preliminary data on levels of cellular DNA damage in grafts produced in two different types of culture medium. Cultures were initiated using corneo-limbal donor tissue after removal of the centr...

Inhibition of sclerostin, a glycoprotein secreted by osteocytes, offers new therapeutic paradigm for treatment of osteoporosis (OP) through its critical role as Wnt/catenin signaling regulator. This study describes the epigenetic regulation of SOST expression in bone biopsies of postmenopausal women. We correlated serum sclerostin, to bone mineral...

Purpose p63 (isoform ΔNp63α) is a putative stemness marker for limbal epithelial stem cells (LESCs), and is essential for the proliferative potential of stem cells in stratified epithelia. The niche for LESCs is the limbus, located between the clear cornea and bulbar conjunctiva. LESCs are responsible for and able to renew and repair the corneal ep...

Adipose tissue-derived stem cells (ASCs) have received considerable attention due to their easy access, expansion potential and differentiation capacity. ASCs are believed to have the potential to differentiate into neurons. However, the mechanisms by which this may occur remain largely unknown. Here, we show that culturing ASCs under active prolif...

Stem cells possess the remarkable property of being able to self-renew and give rise to at least one more differentiated cell type. Embryonic stem cells have the ability to differentiate into all cell types of the body and have unlimited self-renewal potential. Somatic stem cells are found in many adult tissues. They have an extensive but finite li...

Long-term culture of mesenchymal stem cells leads to a loss of differentiation capacity, the molecular mechanism of which remains not understood. We show here that expansion of adipose stem cells (ASCs) to late passage (replicative senescence) is associated with promoter-specific and global changes in epigenetic histone modifications. In undifferen...

SUMMARY: Stem cells have the ability to self-renew, and give rise to one or more differentiated cell types. Embryonic stem cells can differentiate into all cell types of the body and have unlimited self-renewal capacity. Somatic stem cells are found in many adult tissues. They have an extensive but finite lifespan and can differentiate into a more...

The potential use of human mesenchymal stem cells for therapeutic applications implies large scale in vitro culture, increasing the probability of genetic instability and transformation. We examine here the incidence of unbalanced and balanced chromosome rearrangements in polyclonal and single cell-derived cultures of human adipose stem cells to se...

G-banding karyotyping analysis of polyclonal cultures of ASCs. (A) Pc2 at P11. (B) Pc3 at P13. Both karyotypes are normal.

Sample NimbleGen ID No. linking ASC culture and passage number to PDF file providing array CGH profiles for eachchromosome.

Introduction Epigenetic makeup of embryonic stem cells: keeping chromatin loose The epigenetic makeup of mesenchymal stem cells reflects restricted differentiation potential Linking DNA methylation to histone modifications, chromatin packaging and (re)organization of the nuclear compartment Perspectives: towards remodelling the stem cell epigenome?...

Supplementary Figures with legends. The data provided show DNA methylation profiles for adipogenic gene promoters in undifferentiated P4 and senescent ASCs (Supplementary Figure 1), and after three weeks of adipogenic differentiation at P4 and upon senescence (Supplementary Figure 2). Supplementary Figure 3 provides sequencing evidence for a C:T su...

In vivo endothelial commitment of adipose stem cells (ASCs) has scarcely been reported, and controversy remains on the contribution of ASCs to vascularization. We address the epigenetic commitment of ASCs to the endothelial lineage. We report a bisulfite sequencing analysis of CpG methylation in the promoters of two endothelial-cell-specific genes,...

Potential therapeutic use of mesenchymal stem cells (MSCs) is likely to require large-scale in vitro expansion of the cells before transplantation. MSCs from adipose tissue can be cultured extensively until senescence. However, little is known on the differentiation potential of adipose stem cells (ASCs) upon extended culture and on associated epig...

Mesenchymal stem cells (MSCs) have received intense research interest due to their perceived potential application in regenerative medicine; nevertheless, MSCs are primarily restricted to form mesodermal cell types. Adipose stem cells (ASCs) with a CD34+ CD105+ CD45– CD31– immunophenotype can be obtained in an uncultured state with high purity from...

Mesenchymal stem cells from adipose tissue can differentiate into mesodermal lineages. Differentiation potential, however, varies between clones of adipose stem cells (ASCs), raising the hypothesis that epigenetic differences account for this variability. We report here a bisulfite sequencing analysis of CpG methylation of adipogenic (leptin [LEP],...

The functional reprogramming of a differentiated cell to pluripotency may present beneficial applications in regenerative medicine. Somatic cell nuclear transfer may offer this possibility, but technical hurdles and ethical guidelines currently prevent application of this technology in several countries. As a result, alternative approaches are bein...

Stromal stem cells identified in various adult mesenchymal tissues (commonly called mesenchymal stem cells [MSCs]) have in past years received more attention as a result of their potential interest as replacement cells in regenerative medicine. An abundant and easily accessible source of adult human MSCs are stem cells harvested from liposuction ma...

Functional reprogramming of a differentiated cell toward pluripotency may have long-term applications in regenerative medicine. We report the induction of dedifferentiation, associated with genomewide programming of gene expression and epigenetic reprogramming of an embryonic gene, in epithelial 293T cells treated with an extract of undifferentiate...