Implementation of a Protocol for the Transdifferentiation of Buccal Mucosal Epithelium Into Corneal Epithelium
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 4
- 试验地点
- 2
- 主要终点
- Successful Transdifferentiation
研究概览
简要总结
Objectives The transparent surface of the eye, called the cornea, plays a crucial role in transmitting light to the retina and in protecting the eye. On its external surface, the cornea is composed of a constantly renewing multistratified epithelium. This mechanism is fueled by stem cells located in the limbus (the transition zone between the cornea and the sclera). Limbal Stem Cell Deficiency (LSCD) is characterized by a decrease or cessation of epithelial renewal and neovascularization of the cornea. Consequently, the cornea loses its integrity and transparency. This visually impairing condition is currently in a therapeutic impasse as only autologous limbal or allogeneic corneal grafts are viable options, but they pose significant risks to patients.
Studies have shown that the oral cavity contains stem cells that can be isolated, cultured, and transdifferentiated into limbal stem cells (LSCs). However, to date, these studies are limited, and no protocol has been validated. In this study, the advantage of the accessibility of the oral cavity is used to develop a protocol for differentiating cells from the oral mucosa into limbal stem cells (LSCs) for use in a future clinical trial with patients.
Methodology This prospective monocentric study will be conducted on patients from the ophthalmology department of the Montpellier University Hospital who have an indication for conjunctival reconstruction. After obtaining consent from the patients, cells from the oral wall will be sent to the tissue bank of the Montpellier University Hospital, where they will be cultured. Finally, the transdifferentiation steps will be analyzed by the "Eye" research team at the Institute of Neuroscience in Montpellier, which is collaborating on the project. The investigators have established objective factors to assess the success of the developed protocol based on the literature : (i) > 3% of stem cells in primary cultures, (ii) <10% aborted colonies, (iii) Expression of LSC markers (Pax6, Krt14, p63).
详细描述
- Recall on Corneal Anatomy and Histology
The cornea is an essential ocular component for vision: often referred to as the first "transparent porthole" at the front of the eye. It is the first structure that light encounters upon entering the eye. Its primary role is to converge incident light rays, which then proceed towards the lens before reaching the retina and initiating the visual cascade.
The cornea is an avascular and transparent tissue composed of five layers: corneal epithelium, Bowman's layer, corneal stroma, Descemet's membrane, and corneal endothelium.
- The corneal epithelium is the outermost layer of the cornea, consisting of corneal epithelial cells, accounting for about 10% of the entire cornea. This layer constantly regenerates, with complete renewal occurring every seven days. Scratches on this layer generally heal well.
- The Bowman's layer helps bind the corneal epithelium and stroma together. This layer cannot regenerate once damaged, potentially leading to permanent scars that can affect vision.
- The corneal stroma represents about 90% of the cornea and is composed of collagen and keratocytes.
- Descemet's membrane is made up of collagen and separates the corneal stroma from the endothelium. This layer gradually thickens with age.
- The corneal endothelium is the innermost layer and aids in transporting fluid from other corneal layers. Damage to this layer can compromise this process and negatively impact a person's vision.
- Renewal and Healing Process of Corneal Epithelium
Corneal epithelial cells regenerate within 3 to 10 days through constant renewal from limbal stem cells located at the limbus (transition zone between the cornea and sclera) in the basal cell layer, within pigmented crypts called Vogt's palisades.
Deficiency In Limbal Stem Cells (LSCD) is characterized by a loss or impairment of limbal stem cells crucial for corneal epithelial repopulation and limbal barrier function.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Presenting an indication for conjunctival reconstruction using oral mucosa (for example because of a recurrent pterygium, conjunctival carcinoma or ocular burn)
- •Written consent to participate in this research
排除标准
- •Chronic infection (HIV, hepatitis, tuberculosis, Lyme disease)
- •Oral pathology which could affect the health of the oral mucosa tissue according to the opinion of the investigating doctor
- •Uncontrolled systemic disease
- •Pregnant or breastfeeding
结局指标
主要结局
Successful Transdifferentiation
时间窗: change over time between Baseline and 14 days
Successful differentiation, defined by the percentage of stem cells on primary cultures ≥ 3%
次要结局
未报告次要终点