Clinical Trials of Limbal Stem Cell Deficiency Treated with Oral Mucosal Epithelial Cells

The corneal surface is an essential organ necessary for vision, and its clarity must be maintained. The corneal epithelium is renewed by limbal stem cells, located in the limbus and in palisades of Vogt. Palisades of Vogt maintain the clearness of the corneal epithelium by blocking the growth of conjunctival epithelium and the invasion of blood vessels over the cornea. The limbal region can be damaged by chemical burns, physical damage (e.g., by contact lenses), congenital disease, chronic inflammation, or limbal surgeries. The degree of limbus damage is associated with the degree of limbal stem cells deficiency (partial or total). For a long time, the only treatment to restore vision was grafting part of the healthy cornea from the other eye of the patient or by transplanting a cornea from cadavers. The regenerative medicine and stem cell therapies have been applied to restore normal vision using different methodologies. The source of stem cells varies from embryonic stem cells, mesenchymal stem cells, to induced pluripotent stem cells. This review focuses on the use of oral mucosa epithelial stem cells and their use in engineering cell sheets to treat limbal stem cell deficient patients.

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Current approaches to the problem of carrier selection for limbal stem cells cultivation in the treatment of limbal stem cell deficiency

Ophthalmology journal ◽

10.17816/ov11248-56 ◽

2018 ◽

Vol 11 (2) ◽

pp. 48-56 ◽

Cited By ~ 1

Author(s):

Alexey N. Kulikov ◽

Sergey V. Churashov ◽

Valeriy F. Chernysh ◽

Miralda I. Blinova ◽

Olga I. Alexandrova ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Ocular Surface ◽

Contact Lenses ◽

Ex Vivo ◽

Limbal Stem Cell Deficiency ◽

Epithelial Stem Cells ◽

Limbal Stem Cells ◽

Carrier Selection ◽

Limbal Stem Cell

Diseases and damages of the ocular surface are one of the common causes of decreased vision and blindness. Dysfunction or death of limbal epithelial stem cells (LESC) plays an important role in the development of pathological processes in these conditions, which leads to the development of the limbal stem cell deficiency (LSCD). Currently, one of the methods to treat LSCD is a transplantation of cultured ex vivo LESC. The most common carriers for the cultivation of LESC in the world is the amniotic membrane (AM). However, the presence of certain disadvantages in using AM for the cultivation of LESC compels to search new types of carriers made from biological or synthetic materials. In this review, we have analyzed various types of carriers: collagen, fibrin, chitosan with gelatin, silk fibroin, keratin, contact lenses, polylactide-co-glycolide, polycaprolactone, and the possibility of their application as carriers for the LESC cultivation followed by transplantation on the ocular surface is considered.

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

Russian Ophthalmological Journal ◽

10.21516/2072-0076-2019-12-1-103-111 ◽

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.

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Limbal Stem Cell Transplantation: Clinical Results, Limits, and Perspectives

Stem Cells International ◽

10.1155/2018/8086269 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 15

Author(s):

Marta Sacchetti ◽

Paolo Rama ◽

Alice Bruscolini ◽

Alessandro Lambiase

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Corneal Epithelium ◽

Clinical Results ◽

Limbal Stem Cells ◽

Fellow Eye ◽

Ocular Surface Reconstruction ◽

Limbal Stem Cell Transplantation ◽

Limbal Stem Cell

Limbal stem cell deficiency (LSCD) is a clinical condition characterized by damage of cornea limbal stem cells, which results in an impairment of corneal epithelium turnover and in an invasion of the cornea by the conjunctival epithelium. In these patients, the conjunctivalization of the cornea is associated with visual impairment and cornea transplantation has poor prognosis for recurrence of the conjunctivalization. Current treatments of LSCD are aimed at replacing the damaged corneal stem cells in order to restore a healthy corneal epithelium. The autotransplantation of limbal tissue from the healthy, fellow eye is effective in unilateral LSCD but leads to depauperation of the stem cell reservoir. In the last decades, novel techniques such as cultivated limbal epithelial transplantation (CLET) have been proposed in order to reduce the damage of the healthy fellow eye. Clinical and experimental evidence showed that CLET is effective in inducing long-term regeneration of a healthy corneal epithelium in patients with LSCD with a success rate of 70%–80%. Current limitations for the treatment of LSCD are represented by the lack of a marker able to unequivocally identify limbal stem cells and the treatment of total, bilateral LSCD which requires other sources of stem cells for ocular surface reconstruction.

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

Biomedicines ◽

10.3390/biomedicines9091134 ◽

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.

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Limbal Stem Cell-Sparing Corneoscleroplasty with Peripheral Intralamellar Tuck: A New Surgical Technique for Keratoglobus

Case Reports in Ophthalmology ◽

10.1159/000471789 ◽

2017 ◽

Vol 8 (1) ◽

pp. 279-287

Author(s):

Elias Jarade ◽

Rafic Antonios ◽

Sylvain el-Khoury

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Structural Integrity ◽

Single Step ◽

Limbal Stem Cells ◽

Host Cornea ◽

Limbal Stem Cell ◽

The Right ◽

New Surgical Technique

Purpose: To describe the technique of limbal stem cell-sparing corneoscleroplasty for the management of advanced keratoglobus. Methods: A patient with bilateral advanced keratoglobus, with best-corrected visual acuity of 20/400 in the right eye and 20/200 in the left eye, underwent limbal stem cell-sparing corneoscleroplasty of the right eye. Initially, a 360-degree limbal incision with 200-μm depth was created, followed by a sublimbal tunnel dissection into the sclera, in order to conserve stem cells. Next, a limbus-to-limbus lamellar keratectomy at 200-μm depth was performed. Meanwhile, a donor corneoscleral button with preserved endothelium of the central 8 mm was fashioned. Prior to suturing the donor corneoscleral graft using a modified suturing technique to cover its scleral component, a full-thickness trephination of 8-mm diameter was completed in the central host cornea. Results: Reepithelialization occurred within the first week. No episodes of rejection, intraocular pressure spikes, or epithelial breakdown were observed postoperatively. At the 6-month follow-up, the patient had 20/70 best-corrected vision and a smooth cornea with regular astigmatism on topography. Conclusion: Limbal stem cell-sparing corneoscleroplasty is a single-step technique for restoring the structural integrity of the cornea in advanced keratoglobus while preserving the host limbal stem cells.

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Stem Cell-Like Characteristics of Corneal Epithelial Cells

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.998-999.312 ◽

2014 ◽

Vol 998-999 ◽

pp. 312-315

Author(s):

Fan Wang ◽

Bo Ren ◽

Yi Ning Yan

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Epithelial Cells ◽

Corneal Epithelium ◽

Cell Activity ◽

Stem Cell Marker ◽

Corneal Tissue ◽

Limbal Stem Cells ◽

Corneal Epithelial Cells ◽

Corneal Epithelial

Purpose: The adult corneal epithelium is maintained by a population of limbal stem cells (LSCs), transmembrane protein prominin, regarded as stem cell marker was investigated on mouse corneal tissue, to study weather contains CD133-expressing cells and their distribution. Methods: Enucleated mouse eyes were embedded in OCT and cryosections were performed for mmunohistochemical studies using the avidin-biotin-peroxidase complex (ABC) procedure. Meanwhile, dissected mouse corneas were analyzed by westernblot. Results: In the adult mouse, 13A4 immunoreactivity was detected at the apical side of superficial corneal epithelium, including the limbus region, but not by stroma and endothelium. 115 KDa protein was approved in corneal tissue by Westernblot. Conclusions: The stem cell activity does not occur along the limbus but presumably presented by small portion of corneal epithelial cells which may hold a similar properties of stem cells.

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Embryonic stem cells in companion animals (horses, dogs and cats): present status and future prospects

Reproduction Fertility and Development ◽

10.1071/rd07039 ◽

2007 ◽

Vol 19 (6) ◽

pp. 740 ◽

Cited By ~ 23

Author(s):

R. Tayfur Tecirlioglu ◽

Alan O. Trounson

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Embryonic Stem Cell ◽

Nuclear Transfer ◽

Companion Animals ◽

Embryonic Stem ◽

Reproductive Technologies ◽

Specific Cell ◽

Economic Implications ◽

Cell Therapies

Reproductive technologies have made impressive advances since the 1950s owing to the development of new and innovative technologies. Most of these advances were driven largely by commercial opportunities and the potential improvement of farm livestock production and human health. Companion animals live long and healthy lives and the greatest expense for pet owners are services related to veterinary care and healthcare products. The recent development of embryonic stem cell and nuclear transfer technology in primates and mice has enabled the production of individual specific embryonic stem cell lines in a number of species for potential cell-replacement therapy. Stem cell technology is a fast-developing area in companion animals because many of the diseases and musculoskeletal injuries of cats, dogs and horses are similar to those in humans. Nuclear transfer-derived stem cells may also be selected and directed into differentiation pathways leading to the production of specific cell types, tissues and, eventually, even organs for research and transplantaton. Furthermore, investigations into the treatment of inherited or acquired pathologies have been performed mainly in mice. However, mouse models do not always faithfully represent the human disease. Naturally occurring diseases in companion animals can be more ideal as disease models of human genetic and acquired diseases and could help to define the potential therapeutic efficiency and safety of stem cell therapies. In the present review, we focus on the economic implications of companion animals in society, as well as recent biotechnological progress that has been made in horse, dog and cat embryonic stem cell derivation.

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