Understanding cornea epithelial stem cells and stem cell deficiency: Lessons learned using vertebrate model systems

genesis ◽  
2021 ◽  
Vol 59 (1-2) ◽  
Author(s):  
Mohd Tayyab Adil ◽  
Jonathan J. Henry
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Lessons Learned ◽  
Model Systems ◽  
Epithelial Stem Cells ◽  
Vertebrate Model

scholarly journals Stem Cells in the Path of Light, from Corneal to Retinal Reconstruction

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 873
Author(s):  
Ovidiu Samoila ◽  
Lacramioara Samoila
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Clinical Success ◽  
Corneal Stroma ◽  
Cell Transplant ◽  
Inclusion Criteria ◽  
Epithelial Stem Cells ◽  
Corneal Epithelial ◽  
Stem Cells Transplantation ◽  
Limbal Epithelial Stem Cells

The future of eye reconstruction invariably includes stem cells transplantation. Corneal limbus, corneal stroma, trabeculum, retinal cells, optic nerve, and all structures that are irreversibly damaged and have no means to be repaired or replaced, through conventional treatment or surgery, represent targets for stem cell reconstruction. This review tries to answer the question if there is any clinical validation for stem therapies, so far, starting from the cornea and, on the path of light, arriving to the retina. The investigation covers the last 10 years of publications. From 2385 published sources, we found 56 clinical studies matching inclusion criteria, 39 involving cornea, and 17 involving retina. So far, corneal epithelial reconstruction seems well validated clinically. Enough clinical data are collected to allow some form of standardization for the stem cell transplant procedures. Cultivated limbal epithelial stem cells (CLET), simple limbal epithelial transplant (SLET), and oral mucosa transplantation are implemented worldwide. In comparison, far less patients are investigated in retinal stem reconstructions, with lower anatomical and clinical success, so far. Intravitreal, subretinal, and suprachoroidal approach for retinal stem therapies face specific challenges.

Distribution of amniotic stem cells in human term amnion membrane

Microscopy ◽  
2021 ◽  
Author(s):  
Nobuyuki Koike ◽  
Jun Sugimoto ◽  
Motonori Okabe ◽  
Kenichi Arai ◽  
Makiko Nogami ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Markers ◽  
Epithelial Stem Cells ◽  
Human Amnion ◽  
Transporter Protein ◽  
Amniotic Mesenchymal Stem Cells ◽  
Amnion Membrane ◽  
And Function ◽  
A Site

Abstract Amnion membrane studies related to miscarriage have been conducted in the field of obstetrics and gynecology. However, the distribution of stem cells within the amnion and the differences in the properties of each type of stem cells are still not well understood. We address this gap in knowledge in the present study where we morphologically classified the amnion membrane, and we clarified the distribution of stem cells here to identify functionally different amniotic membrane–derived stem cells. The amnion can be divided into a site that is continuous with the umbilical cord (region A), a site that adheres to the placenta (region B), and a site that is located opposite the placenta (region C). We found that human amnion epithelial stem cells (HAECs) that strongly express stem cell markers were abundant in area A. HAEC not only expressesed stem cell-specific surface markers TRA-1-60, Tra-1-81, SSEA4, SSEA3, but was also OCT-3/4 positive and had alkaline phosphatase activity. Human amniotic mesenchymal stem cells expressed KLF-A, OCTA, Oct3/4, c-MYC and Sox2 which is transcription factor. Especially, in regions A and B they have expressed CD73, and the higher expression of BCRP which is drug excretion transporter protein than the other parts. These data suggest that different types of stem cells may have existed in different area. The understanding the relation with characteristics of the stem cells in each area and function would allow for the efficient harvest of suitable HAE and HAM stem cells as using tool for regenerative medicine.

scholarly journals Derivation and Characterization of EGFP-Labeled Rabbit Limbal Mesenchymal Stem Cells and Their Potential for Research in Regenerative Ophthalmology

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1134
Author(s):  
Julia I. Khorolskaya ◽  
Daria A. Perepletchikova ◽  
Daniel V. Kachkin ◽  
Kirill E. Zhurenkov ◽  
Elga I. Alexander-Sinkler ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Fluorescent Protein ◽  
Rabbit Model ◽  
Stem Cell Markers ◽  
Epithelial Stem Cells ◽  
Limbal Stem Cell ◽  
Green Fluorescent

The development of cell-based approaches to the treatment of various cornea pathologies, including limbal stem cell deficiency (LSCD), is an area of current interest in regenerative biomedicine. In this context, the shortage of donor material is urgent, and limbal mesenchymal stem cells (L-MSCs) may become a promising cell source for the development of these novel approaches, being established mainly within the rabbit model. In this study, we obtained and characterized rabbit L-MSCs and modified them with lentiviral transduction to express the green fluorescent protein EGFP (L-MSCs-EGFP). L-MSCs and L-MSCs-EGFP express not only stem cell markers specific for mesenchymal stem cells but also ABCG2, ABCB5, ALDH3A1, PAX6, and p63a specific for limbal epithelial stem cells (LESCs), as well as various cytokeratins (3/12, 15, 19). L-MSCs-EGFP have been proven to differentiate into adipogenic, osteogenic, and chondrogenic directions, as well as to transdifferentiate into epithelial cells. The possibility of using L-MSCs-EGFP to study the biocompatibility of various scaffolds developed to treat corneal pathologies was demonstrated. L-MSCs-EGFP may become a useful tool for studying regenerative processes occurring during the treatment of various corneal pathologies, including LSCD, with the use of cell-based technologies.

Histological analysis of epithelial stem cells during induced pluripotent stem cell-derived teratoma development

2012 ◽  
Vol 54 (1) ◽  
pp. 58-65 ◽  
Author(s):  
Ryota Kishigami ◽  
Keishi Otsu ◽  
Ai Oikawa-Sasaki ◽  
Naoki Fujiwara ◽  
Kiyoto Ishizeki ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Histological Analysis ◽  
Induced Pluripotent Stem Cell ◽  
Epithelial Stem Cells ◽  
Induced Pluripotent

scholarly journals Characterization of putative stem cells in isolated human colonic crypt epithelial cells and their interactions with myofibroblasts

2009 ◽  
Vol 296 (2) ◽  
pp. C296-C305 ◽  
Author(s):  
S. Samuel ◽  
R. Walsh ◽  
J. Webb ◽  
A. Robins ◽  
C. Potten ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Epithelial Cells ◽  
Side Population ◽  
Cell Types ◽  
Population Characteristics ◽  
Colonic Crypt ◽  
Epithelial Stem Cells ◽  
Colonic Crypts ◽  
Cell Niche

Colonic epithelial stem cells are believed to be located at the crypt base where they have previously been shown to express musashi-1. The colonic stem cell niche, which includes extracellular matrix and myofibroblasts (together with other cell types), is likely to be important in maintaining the function of the progenitor cells. The aims of our studies were to characterize stem cells in isolated and disaggregated human colonic crypt epithelial cells and investigate their interactions with monolayers of primary human colonic myofibroblasts. In unfractionated preparations of disaggregated colonic crypts, musashi-1 positive cells preferentially adhered to colonic myofibroblasts, despite the presence of excess blocking anti-β1-integrin antibody. These adherent epithelial cells remained viable for a number of days and developed slender processes. Cells with side population characteristics (as demonstrated by ability to expel the dye Hoechst 33342) were consistently seen in the isolated colonic crypt epithelial cells. These side population cells expressed musashi-1, β1-integrin, BerEP4, and CD133. Sorted side population crypt epithelial cells also rapidly adhered to primary colonic myofibroblasts. In conclusion, in preparation of isolated and disaggregated human colonic crypts, cells with stem cell characteristics preferentially adhere to primary human colonic myofibroblasts in a β1-integrin-independent fashion.

scholarly journals Limbal stem cell deficiency: etiology, pathogenesis, priniciples and prospects of surgical treatment

2019 ◽  
Vol 12 (1) ◽  
pp. 103-111
Author(s):  
A. S. Dubovikov ◽  
I. O. Gavrilyuk ◽  
A. N. Kulikov ◽  
S. V. Churashov ◽  
V. F. Chernysh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Surgical Treatment ◽  
Ex Vivo ◽  
Epithelial Stem Cells ◽  
Limbal Stem Cells ◽  
History Of Development ◽  
History Of ◽  
Limbal Epithelial Stem Cells ◽  
Limbal Stem Cell

The review is focused on the modern view of the etiology and pathogenesis of limbal stem cells deficiency. The history of development of tissue and ex-vivo transplantation of limbal epithelial stem cells is presented. Certain promising directions of the treatment of patients with limbal stem cells deficiency are presented.

scholarly journals EGFR signaling promotes self-renewal through the establishment of cell polarity in Drosophila follicle stem cells

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Angela Castanieto ◽  
Michael J Johnston ◽  
Todd G Nystul
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Polarity ◽  
Growth Factor Receptor ◽  
Egfr Signaling ◽  
Epithelial Stem Cells ◽  
Cell Fates ◽  
Liver Kinase B1 ◽  
Follicle Stem Cells ◽  
Drosophila Ovary

Epithelial stem cells divide asymmetrically, such that one daughter replenishes the stem cell pool and the other differentiates. We found that, in the epithelial follicle stem cell (FSC) lineage of the Drosophila ovary, epidermal growth factor receptor (EGFR) signaling functions specifically in the FSCs to promote the unique partially polarized state of the FSC, establish apical–basal polarity throughout the lineage, and promote FSC maintenance in the niche. In addition, we identified a novel connection between EGFR signaling and the cell-polarity regulator liver kinase B1 (LKB1), which indicates that EGFR signals through both the Ras–Raf–MEK–Erk pathway and through the LKB1–AMPK pathway to suppress apical identity. The development of apical–basal polarity is the earliest visible difference between FSCs and their daughters, and our findings demonstrate that the EGFR-mediated regulation of apical–basal polarity is essential for the segregation of stem cell and daughter cell fates.

scholarly journals Endometrial Stem Cell Markers: Current Concepts and Unresolved Questions

2018 ◽  
Vol 19 (10) ◽  
pp. 3240 ◽  
Author(s):  
Nicola Tempest ◽  
Alison Maclean ◽  
Dharani Hapangama
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Treatment Strategies ◽  
Human Endometrium ◽  
Current Evidence ◽  
Stem Cell Markers ◽  
Epithelial Stem Cells ◽  
Functional Layer ◽  
Almost All ◽  
Stromal Stem Cells

The human endometrium is a highly regenerative organ undergoing over 400 cycles of shedding and regeneration over a woman’s lifetime. Menstrual shedding and the subsequent repair of the functional layer of the endometrium is a process unique to humans and higher-order primates. This massive regenerative capacity is thought to have a stem cell basis, with human endometrial stromal stem cells having already been extensively studied. Studies on endometrial epithelial stem cells are sparse, and the current belief is that the endometrial epithelial stem cells reside in the terminal ends of the basalis glands at the endometrial/myometrial interface. Since almost all endometrial pathologies are thought to originate from aberrations in stem cells that regularly regenerate the functionalis layer, expansion of our current understanding of stem cells is necessary in order for curative treatment strategies to be developed. This review critically appraises the postulated markers in order to identify endometrial stem cells. It also examines the current evidence supporting the existence of epithelial stem cells in the human endometrium that are likely to be involved both in glandular regeneration and in the pathogenesis of endometrial proliferative diseases such as endometriosis and endometrial cancer.

GMP-compliant Manufacturing Process of an Advanced Therapy Medicinal Product Based on Conjunctival Epithelial Cells

2020 ◽  
Author(s):  
Marina Bertolin ◽  
Stefano Ferrari ◽  
Claudia Breda ◽  
Barbara Ferrari ◽  
Diego Ponzin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Quality Control ◽  
Stem Cell ◽  
Medicinal Product ◽  
Manufacturing Process ◽  
Manufacturing Processes ◽  
Epithelial Stem Cells ◽  
Advanced Therapy Medicinal Product ◽  
Advanced Therapy ◽  
Conjunctival Epithelial Cells

Abstract Background. Conjunctival epithelial stem cell therapy represents a potential and valuable therapeutic option for people suffering from conjunctival disorders. We recently developed a research protocol for the ex vivo cultivation of conjunctival epithelial cells. However, manufacturing and release of any Advanced Therapy Medicinal Product (ATMP) must be designed and planned according to the Good Manufacturing Practices (GMPs) guidelines. GMPs require the development and validation of properly defined manufacturing processes, analysis methods and process validations. Our previous experience with GMP-cultured corneal epithelial stem cells for clinical application on patients with limbal stem cell deficiency led us to set up a protocol for cultivation of conjunctival cells with standards complying with the requests for clinical studies. The major challenge for cell-based products is to develop manufacturing processes while maintaining the critical quality parameters in terms of safety, identity, purity and potency.Results. The manufacturing process was re-designed in order to include all the quality control assays needed for the release of any ATMP, i.e., sterility, morphology, cell viability, dose, cell identity and impurities, potency, lack of pyrogens, mycoplasma and viral detection. Methods and acceptance values were set for all the assays. Quality control assays to evaluate safety and efficacy were also investigated.Conclusion. Here, we describe the main phases of the manufacturing process of a conjunctival stem cell-based product to use in clinical applications. Such characterization is crucial for the preparation of documents and dossiers needed by the competent authorities to start a phase I clinical study on patients with conjunctival disorders. The procedure necessary to reach the marketing authorization of such a new cell-based product is still long, but, if reliable and validated, we believe that, in the near future, patients with conjunctival disorders might have a new treatment based on transplantation of autologous cultured conjunctival epithelial stem cells.

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