scholarly journals Corneal Epithelial Stem Cells–Physiology, Pathophysiology and Therapeutic Options

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2302
Author(s):  
Yue Ruan ◽  
Subao Jiang ◽  
Aytan Musayeva ◽  
Norbert Pfeiffer ◽  
Adrian Gericke
Keyword(s):  
Stem Cell ◽  
Vision Loss ◽  
Ex Vivo ◽  
Dyskeratosis Congenita ◽  
Limbal Stem Cell Deficiency ◽  
Therapeutic Options ◽  
Human Cornea ◽  
Epithelial Stem Cells ◽  
Allogenic Stem Cell Transplantation ◽  
Limbal Stem Cell

In the human cornea, regeneration of the epithelium is regulated by the stem cell reservoir of the limbus, which is the marginal region of the cornea representing the anatomical and functional border between the corneal and conjunctival epithelium. In support of this concept, extensive limbal damage, e.g., by chemical or thermal injury, inflammation, or surgery, may induce limbal stem cell deficiency (LSCD) leading to vascularization and opacification of the cornea and eventually vision loss. These acquired forms of limbal stem cell deficiency may occur uni- or bilaterally, which is important for the choice of treatment. Moreover, a variety of inherited diseases, such as congenital aniridia or dyskeratosis congenita, are characterized by LSCD typically occurring bilaterally. Several techniques of autologous and allogenic stem cell transplantation have been established. The limbus can be restored by transplantation of whole limbal grafts, small limbal biopsies or by ex vivo-expanded limbal cells. In this review, the physiology of the corneal epithelium, the pathophysiology of LSCD, and the therapeutic options will be presented.

scholarly journals Preserving Basement Membranes during Detachment of Cultivated Oral Mucosal Epithelial Cell Sheets for the Treatment of Total Bilateral Limbal Stem Cell Deficiency

2018 ◽  
Vol 27 (2) ◽  
pp. 264-274 ◽  
Author(s):  
Marie-Rose Rovere ◽  
Patricia Rousselle ◽  
Marek Haftek ◽  
Bruce Charleux ◽  
Viridiana Kocaba ◽  
...  
Keyword(s):  
Stem Cell ◽  
Vision Loss ◽  
Ex Vivo ◽  
Immunosuppressive Treatment ◽  
Basement Membranes ◽  
Limbal Stem Cell Deficiency ◽  
Type Vii Collagen ◽  
Limbal Stem Cell ◽  
The Impact ◽  
Limbal Transplantation

Total bilateral limbal stem cell deficiency leading to loss of corneal clarity, potential vision loss, pain, photophobia, and keratoplasty failure cannot be treated by autologous limbal transplantation, and allogeneic limbal transplantation requires subsequent immunosuppressive treatment. Cultured autologous oral mucosal epithelial cells have been shown to be safe and effective alternatives. These cells can be transplanted on supports or without support after detachment from the culture dishes. Dispase, known for epidermal sheet detachment, is reported as not usable for oral mucosa. The objective was to find an optimized detachment method providing a sufficiently resistant and adhesive cultured oral mucosal epithelium (COME), which can be grafted without sutures. Enzymatic treatments (dispase or collagenase at different concentrations) were compared to enzyme-free mechanical detachment. Histological immunofluorescence (IF) and Western blotting (WB) were used to examine the impact on adhesion markers (laminin-332, β1-integrin, and type VII collagen) and junctional markers (E-cadherin, P-cadherin). Finally, the COME ability to adhere to the cornea and produce a differentiated epithelium 15 d after grafting onto an ex vivo porcine stroma model were investigated by histology, IF, and transmission electron microscopy. Collagenase at 0.5 mg/mL and dispase at 5 mg/mL were selected for comparative study on adhesive expression marker by IF and WB showed that levels of basement membrane proteins and cell–cell and cell–matrix junction proteins were not significantly different between the 3 detachment methods. Collagenase 0.5 mg/mL was selected for the next step validation because of the better reproducibility, 100% success (vs. 33% with dispase 5 mg/mL). Grafted onto porcine de-epithelialized corneal stroma, collagenase 0.5 mg/mL detached COME were found to adhere, stratify, and continue to ensure renewal of the epithelium. For COME, collagenase 0.5 mg/mL enzymatic detachment was selected and validated on its resistance and adhesive marker expression as well as their anchorage onto our new ex vivo de-epithelialized stroma model.

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

2018 ◽  
Vol 11 (2) ◽  
pp. 48-56 ◽  
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.

Transplantation of Conjunctival Epithelial Cells Cultivated Ex Vivo in Patients With Total Limbal Stem Cell Deficiency

Cornea ◽  
2013 ◽  
Vol 32 (3) ◽  
pp. 221-228 ◽  
Author(s):  
José Reinaldo S. Ricardo ◽  
Priscila C. Cristovam ◽  
Pedro A. N. Filho ◽  
Charles C. Farias ◽  
Aline L. de Araujo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Epithelial Cells ◽  
Ex Vivo ◽  
Limbal Stem Cell Deficiency ◽  
Limbal Stem Cell ◽  
Conjunctival Epithelial Cells

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 Successful Application of Ex Vivo Expanded Human Autologous Oral Mucosal Epithelium for the Treatment of Total Bilateral Limbal Stem Cell Deficiency

Stem Cells ◽  
2014 ◽  
Vol 32 (8) ◽  
pp. 2135-2146 ◽  
Author(s):  
Sai Kolli ◽  
Sajjad Ahmad ◽  
Hardeep Singh Mudhar ◽  
Adam Meeny ◽  
Majlinda Lako ◽  
...  
Keyword(s):  
Stem Cell ◽  
Ex Vivo ◽  
Limbal Stem Cell Deficiency ◽  
Mucosal Epithelium ◽  
Limbal Stem Cell

Limbal stem cell deficiency in patients with inherited stem cell disorder of dyskeratosis congenita

2012 ◽  
Vol 32 (6) ◽  
pp. 615-622 ◽  
Author(s):  
Deniz Aslan ◽  
Rustu F. Akata ◽  
Harriet Holme ◽  
Tom Vulliamy ◽  
Inderjeet Dokal
Keyword(s):  
Stem Cell ◽  
Dyskeratosis Congenita ◽  
Limbal Stem Cell Deficiency ◽  
Limbal Stem Cell ◽  
Cell Disorder
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