scholarly journals Hyaluronan-Based Hydrogel Scaffolds for Limbal Stem Cell Transplantation: A Review

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 245 ◽  
Author(s):  
Mazyar Yazdani ◽  
Aboulghassem Shahdadfar ◽  
Catherine Joan Jackson ◽  
Tor Paaske Utheim
Keyword(s):  
Extracellular Matrix ◽  
Stem Cell ◽  
Limbal Stem Cells ◽  
Receptor Proteins ◽  
Hydrogel Scaffolds ◽  
Cell Based Therapy ◽  
Limbal Stem Cell Transplantation ◽  
Limbal Stem Cell ◽  
Cell Niche ◽  
Synthesis And Degradation

Hyaluronan (HA), also termed hyaluronic acid or hyaluronate, is a major component of the extracellular matrix. This non-sulfated glycosaminoglycan plays a key role in cell proliferation, growth, survival, polarization, and differentiation. The diverse biological roles of HA are linked to the combination of HA’s physicochemical properties and HA-binding proteins. These unique characteristics have encouraged the application of HA-based hydrogel scaffolds for stem cell-based therapy, a successful method in the treatment of limbal stem cell deficiency (LSCD). This condition occurs following direct damage to limbal stem cells and/or changes in the limbal stem cell niche microenvironment due to intrinsic and extrinsic insults. This paper reviews the physical properties, synthesis, and degradation of HA. In addition, the interaction of HA with other extracellular matrix (ECM) components and receptor proteins are discussed. Finally, studies employing HA-based hydrogel scaffolds in the treatment of LSCD are reviewed.

scholarly journals Goals and Challenges of Stem Cell-Based Therapy for Corneal Blindness Due to Limbal Deficiency

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1483
Author(s):  
Margarita Calonge ◽  
Teresa Nieto-Miguel ◽  
Ana de la Mata ◽  
Sara Galindo ◽  
José M. Herreras ◽  
...  
Keyword(s):  
Stem Cell ◽  
Regenerative Medicine ◽  
Stem Cell Niche ◽  
Basic Research ◽  
Cell Based Therapy ◽  
Novel Approach ◽  
Corneal Blindness ◽  
Limbal Stem Cell ◽  
Cell Niche ◽  
The Right

Corneal failure is a highly prevalent cause of blindness. One special cause of corneal failure occurs due to malfunction or destruction of the limbal stem cell niche, upon which the superficial cornea depends for homeostatic maintenance and wound healing. Failure of the limbal niche is referred to as limbal stem cell deficiency. As the corneal epithelial stem cell niche is easily accessible, limbal stem cell-based therapy and regenerative medicine applied to the ocular surface are among the most highly advanced forms of this novel approach to disease therapy. However, the challenges are still great, including the development of cell-based products and understanding how they work in the patient’s eye. Advances are being made at the molecular, cellular, and tissue levels to alter disease processes and to reduce or eliminate blindness. Efforts must be coordinated from the most basic research to the most clinically oriented projects so that cell-based therapies can become an integrated part of the therapeutic armamentarium to fight corneal blindness. We undoubtedly are progressing along the right path because cell-based therapy for eye diseases is one of the most successful examples of global regenerative medicine.

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

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
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.

Autologous Cultivated Limbal Stem Cell Transplantation after Failed Previous Limbal Graft

2017 ◽  
Vol 27 (5) ◽  
pp. e137-e139
Author(s):  
Karl A. Knutsson ◽  
Stanislav Matuska ◽  
Paolo Rama
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Ocular Surface ◽  
Ex Vivo ◽  
Limbal Stem Cells ◽  
Limbal Stem Cell Transplantation ◽  
Limbal Stem Cell ◽  
Contralateral Eye

Purpose To describe a case of unilateral limbal stem cell deficiency (LSCD) with previously failed autologous graft, resolved by ocular surface reconstruction using cultured autologous limbal stem cells from the contralateral eye. Case Report A 35-year-old patient presented to our clinic with LSCD due to a unilateral alkali burn. The patient had received a previous limbal graft from the contralateral eye that had failed to impede corneal conjunctivalization. We decided to repeat limbal stem cell transplantation using an ex vivo cultivation procedure to reduce the risk of tissue harvesting on the healthy fellow eye. A small limbal biopsy (1.5 × 1.5 mm) near the previously excised limbus was performed. Stem cells were then isolated and cultured on fibrin and a 3T3 feeder cell layer using a standard protocol. Four months later, the cultivated cells on fibrin were grafted after pannus removal. In the subsequent months, the ocular surface stabilized and inflammation decreased. Two years later, the patient underwent large tectonic lamellar keratoplasty for severe corneal thinning involving the entire cornea, and 6 months later central penetrating keratoplasty and extracapsular cataract extraction with intraocular lens implantation and pupilloplasty was performed. Following reconstruction, the patient showed improved best-corrected vision from count fingers to 20/200 due to amblyopia, and the ocular surface was stable with a transparent corneal graft. Conclusions Ex vivo limbal stem cell transplantation is a valid technique for treating LSCD and can be utilized for treating patients who have had previous failed limbal grafts.

scholarly journals Effect of Cross-Linking Density on the Structures and Properties of Carbodiimide-Treated Gelatin Matrices as Limbal Stem Cell Niches

2018 ◽  
Vol 19 (11) ◽  
pp. 3294 ◽  
Author(s):  
Jui-Yang Lai ◽  
Li-Jyuan Luo ◽  
David Ma
Keyword(s):  
Surface Roughness ◽  
Stem Cell ◽  
Cross Linking ◽  
Epithelial Tissue ◽  
Human Amniotic Membrane ◽  
Limbal Stem Cells ◽  
Structures And Properties ◽  
Cross Linker ◽  
Limbal Stem Cell ◽  
Stem Cell Niches

Given that human amniotic membrane is a valuable biological material not readily available for corneal epithelial tissue engineering, gelatin is considered as a potential alternative to construct a cellular microenvironment. This study investigates, for the first time, the influence of cross-linking density of carbodiimide-treated gelatin matrices on the structures and properties of artificial limbal stem cell niches. Our results showed that an increase in the carbodiimide concentration from 1.5 to 15 mM leads to an upward trend in the structural and suture strength of biopolymers. Furthermore, increasing number of cross-linking bridges capable of linking protein molecules together may reduce their crystallinity. For the samples treated with 50 mM of cross-linker (i.e., the presence of excess N-substituted carbodiimide), abundant N-acylurea was detected, which was detrimental to the in vitro and in vivo ocular biocompatibility of gelatin matrices. Surface roughness and stiffness of biopolymer substrates were found to be positively correlated with carbodiimide-induced cross-link formation. Significant increases of integrin β1 expression, metabolic activity, and ABCG2 expression were noted as the cross-linker concentration increased, suggesting that the bulk crystalline structure and surface roughness/stiffness of niche attributed to the number of cross-linking bridges may have profound effects on a variety of limbal epithelial cell behaviors, including adhesion, proliferation, and stemness maintenance. In summary, taking the advantages of carbodiimide cross-linking-mediated development of gelatin matrices, new niches with tunable cross-linking densities can provide a significant boost to maintain the limbal stem cells during ex vivo expansion.

scholarly journals Extracellular matrix and the neural stem cell niche

2011 ◽  
Vol 71 (11) ◽  
pp. 1006-1017 ◽  
Author(s):  
Ilias Kazanis ◽  
Charles ffrench-Constant
Keyword(s):  
Extracellular Matrix ◽  
Stem Cell ◽  
Neural Stem Cell ◽  
Stem Cell Niche ◽  
Neural Stem Cell Niche ◽  
Cell Niche

scholarly journals A Review of Limbal Stem Cell Deficiency

2019 ◽  
Vol 2 (1) ◽  
pp. e4-e11
Author(s):  
John E. Conto
Keyword(s):  
Stem Cell ◽  
Contact Lenses ◽  
Systemic Disease ◽  
Anterior Segment ◽  
Treatment Strategies ◽  
Limbal Stem Cell Deficiency ◽  
Contact Lens Wear ◽  
Limbal Stem Cell Transplantation ◽  
Limbal Stem Cell ◽  
Amniotic Membranes

Limbal stem cell deficiency (LSCD) can be secondary to multiple etiologies including contact lens wear, chemical or thermal trauma, and systemic disease, any of which can result in the reduction of the number of stem cells or their decreased functionality. Primary LSCD is seen with a variety of congenital anterior segment disorders. Often LSCD can be stabilized and timely diagnosis is the key. The use of topical corticosteroids and artificial tear lubricants, along with treatment of any underlying conditions, and discontinuation of contact lenses are important initial treatment strategies. Advance treatments include amniotic membranes, limbal stem cell transplantation and keratoprostheses.

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