Limbal Stem-Cell Therapy and Long-Term Corneal Regeneration (original) (raw)
Related papers
2020
Objectives: This study compares the efficacy of stem cell transplantation in corneal regeneration and restoration of the limbic deficit in an experimental chemical burn in rabbits. Methods: The biopsy of limbus and the chemical burn were performed in all rabbits, and the amniotic membranes were obtained from a pregnant rabbit. A control group without transplantation, to study spontaneous and natural healing, and transplanted the stem cells produced in vitro under the corneal epithelium burned. To compare the result, a group was tested for amniotic stem cell transplantation, a group for limbal stem cell graft, and another group for combined transplantation of both types of stem cells. Results: Transplanted rabbits develop permanent unilateral blindness due to a severe limbic deficit. The group receiving only amniotic stem cells shows temporary anatomical improvement without functional recovery. The two groups receiving limbal stem cells alone or combined with amniotic stem cells show...
Clinical & Experimental Ophthalmology, 2012
Chemical burns cause depletion of limbal stem cells and eventually lead to corneal opacity and visual loss. We investigated the long-term effectiveness of autologous cultured limbal stem cell grafts in patients with limbal stem cell deficiency. Prospective, non-comparative interventional case series. Sixteen eyes from 16 patients with severe, unilateral limbal stem cell deficiency caused by chemical burns. Autologous ex vivo cultured limbal stem cells were grafted onto the recipient eye after superficial keratectomy. Clinical parameters of limbal stem cell deficiency (stability/transparency of the corneal epithelium, superficial corneal vascularization and pain/photophobia), visual acuity, cytokeratin expression on impression cytology specimens and histology on excised corneal buttons. At 12 months post-surgery, evaluation of the 16 patients showed that 10 (62.6%) experienced complete restoration of a stable and clear epithelium and 3 (18.7%) had partially successful outcomes (re-appearance of conjunctiva in some sectors of the cornea and instable corneal surface). Graft failure (no change in corneal surface conditions) was seen in three (18.7%) patients. Penetrating keratoplasty was performed in seven patients, with visual acuity improving up to 0.8 (best result). For two patients, regeneration of the corneal epithelium was confirmed by molecular marker (p63, cytokeratin 3, 12 and 19, mucin 1) analysis. Follow-up times ranged from 12 to 50 months. Grafts of autologous limbal stem cells cultured onto fibrin glue discs can successfully regenerate the corneal epithelium in patients with limbal stem cell deficiency, allowing to perform successful cornea transplantation and restore vision.
Regenerative Approaches and Future Trends for the Treatment of Corneal Burn Injuries
Journal of Clinical Medicine, 2021
Ocular chemical and thermal burns are frequent causes of hospitalization and require immediate interventions and care. Various surgical and pharmacological treatment strategies are employed according to damage severity. Controlling inflammation and neovascularization while promoting normal ocular surface anatomy and function restoration is the principal aim. In the most severe cases, when epithelial healing is severely affected, reconstruction of the ocular surface may be a valid option, which, however, requires expertise, adequate instruments, and qualified donors. Numerous endogenous and exogenous strategies have been considered for corneal repair. Among these, stem cells and their derivatives have offered numerous attractive possibilities in finding an effective way in stimulating corneal regeneration. Limbal epithelial stem cells and mesenchymal cells from the ocular tissue as well as from various sources have demonstrated their effectiveness in dampening neovascularization, sca...
Concise review: the coming of age of stem cell treatment for corneal surface damage
Stem cells translational medicine, 2014
The cornea is a vital component of the eye because it provides approximately 70% of the refraction and focusing of incoming light. Being the outermost surface of the eye, it faces continuous stress from dryness, photodamage, infection, and injury; however, like the skin, the cornea regularly refreshes itself by shedding its epithelial cells, which are readily replaced, keeping the ocular surface stable and functional. This regular turnover of the corneal epithelial cells occurs through the stem cells in the limbus, an annular ring of a tissue surrounding the cornea, separating it from the sclera and the conjunctival membrane. The loss of this reserve of stem cells leads to a condition called limbal stem cell deficiency. Treatment for this disorder has evolved from transplanting whole limbal tissues to the affected eye to transplanting laboratory cultured limbal cells. This procedure is called cultivated limbal epithelial transplantation (CLET). Since its start in 1997, more than 1,0...
Journal of EuCornea, 2019
To report a case of corneal epithelial restoration after penetrating keratoplasty following multiple complications in repeated failed cultivated stem cell grafts. Methods: This is a case report of a 62-year old patient who was treated for unilateral severe limbal stem cell deficiency after a chemical burn of the right eye. Results: Two attempts to reconstruct the ocular surface using autologous cultivated limbal stem cell grafts (CLET) failed, and were complicated by perforations requiring two emergency penetrating keratoplasties. While the first donor cornea revascularised quickly, the corneal epithelium of the second remained transparent, avascular and stable until one year postoperatively. In vivo confocal microscopic examination confirmed presence of a healthy corneal epithelial phenotype. Conclusions: Occurrence of serious adverse events are related to an inadequate epithelial homeostasis following CLET. The mechanisms of action of limbal stem cell transplantation are still poorly understood and the corneal epithelial integrity may be maintained without limbal input.
Cultivated Limbal Epithelial Transplantation in Children With Ocular Surface Burns
JAMA Ophthalmology, 2013
Importance: Although several reports are available on the use of conventional and cultured limbal epithelium using various substrates in the treatment of limbal stem cell deficiency (LSCD), the patient populations studied have been largely adults. Thus, to our knowledge, the outcomes of this procedure exclusively in a pediatric population have not been reported previously. Objective: To report the outcomes of autologous ex vivo cultivated limbal epithelial transplantation (CLET) in pediatric patients with LSCD after ocular burns.
Repairing the corneal epithelium using limbal stem cells or alternative cell-based therapies
Expert opinion on biological therapy, 2018
The corneal epithelium is maintained by limbal stem cells (LSCs) that reside in the basal epithelial layer of the tissue surrounding the cornea termed the limbus. Loss of LSCs results in limbal stem cell deficiency (LSCD) that can cause severe visual impairment. Patients with partial LSCD may respond to conservative therapies designed to rehabilitate the remaining LSCs. However, if these conservative approaches fail or, if complete loss of LSCs occurs, transplantation of LSCs or their alternatives is the only option. While a number of clinical studies utilizing diverse surgical and cell culture techniques have shown favorable results, a universal cure for LSCD is still not available. Knowledge of the potential risks and benefits of current approaches, and development of new technologies, is essential for further improvement of LSCD therapies. Areas covered: This review focuses on cell-based LSCD treatment approaches ranging from current available clinical therapies to preclinical st...
Chapter 5 Limbal Stem Cells: Application in Ocular Biomedicine
International review of cell and molecular biology
Corneal opacification due to limbal stem cell deficiency (LSCD) is an important cause for ocular morbidity, resulting from a number of intrinsic and extrinsic factors. While the extrinsic factors include conditions such as chemical or thermal injuries, intrinsic include dysfunction, or reduction in the number of stem cells either due to pathological changes in autoimmune diseases or secondary to certain clinical conditions such as diabetes, dry eye disorders, or multiple previous eye surgeries. LSCD is characterized by a classic triad of signs—conjunctivalization, neovascularization and decrease in vision. With the increasing knowledge of limbal stem cells, the treatment of this condition has evolved from simple debridement to use of biological materials, direct transplantation of the healthy limbal tissue from the contralateral eye, or allogenic source to the use of cultivated limbal epithelial sheets. This chapter provides an update on the disease pathology, various treatment meth...
2002
Purpose. To describe the histopathologic changes in the cornea following amniotic membrane transplantation (AMT) combined with limbal transplantation. Methods. Four eyes with complete limbal stem cell deficiency after severe chemical burn underwent AMT with either a living-related conjunctival limbal allograft (lr-CLAL) (three eyes) or a conjunctival limbal autograft (CLAU) (one eye) for ocular surface reconstruction. Penetrating kerato-plasty was performed several months after the initial procedure for further visual rehabilitation. Mean follow up time was 20 months. Light and transmission electron microscopy (TEM) and indirect immunofluorescence microscopy of the excised corneal buttons were performed. Results. All specimens displayed a multilayered epithelium without conjunctival goblet cells over the entire corneal surface. Basal epithelial cells demonstrated a firm connection to the remnants of the transplanted amniotic membrane (AM), which at some places appeared to be in a state of "modification" or "remodeling" in the collagen layers. The basement membrane zone displayed a positive staining when using antibodies against colla-gen IV and VII, integrin ␣6 and 4, laminin 5, and bullous pem-phigoid antigen 2. Remnants of the AM in the specimen showed staining of collagen IV, which was found also in cross-sections of cryopreserved AM. The recipients Bowman's membranes that were only partially present after the initial trauma were significantly disturbed. Conclusion. Within the time frame studied, the transplanted AM apparently survives and integrates into the host tissue being modified or remodeled by recipient cells. AMT in combination with a CLAU or lr-CLAL is a useful technique in promoting a rapid and stable reepithelialization of a corneal surface following severe chemical or thermal damage. NB added: The ACADEMIA.edu-upload-System DOES NOT allow to insert FIRST AUTHOR('s) or Co-Authors' names even if they CANNOT have an official / institutional e-mail-address due to their retirement or leaving academic institution.