A Clinical Study on Co-transplantation of Autologous Limbal Stem Cells and Corneal Stromal Stem Cells to Repair Corneal Injury: an Open-label, Randomized Clinical Trial
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 60
- 主要终点
- Vision
研究概览
简要总结
This study aims to: 1) verify the feasibility of treating limbal stem cell deficiency (LSCD) caused by chemical injury with autologous limbal stem cell transplantation combined with corneal stromal stem cell transplantation; 2) evaluate the corneal healing patterns following autologous stem cell transplantation; and 3) establish a clinical intervention protocol based on autologous corneal stem cell transplantation. Sixty cases of single-eye LSCD were included.
详细描述
Limbal Stem Cells (LSCs) are the sole source of corneal epithelial self-renewal and play a critical role in maintaining corneal transparency. Chemical or physical injury to the eye and inflammation can lead to limbal stem cell deficiency (LSCD), accompanied by a series of pathological changes, such as irreversible fibrosis of corneal stromal cells and neovascularization, ultimately resulting in blindness. The fundamental solution for such diseases is the replenishment of LSCs to reconstruct a functional cornea. However, traditional treatment methods, such as corneal transplantation, face bottlenecks, including a severe shortage of corneal donors and the risk of immune rejection. Additionally, donor corneas do not contain LSCs, making it impossible to reconstruct the patient's limbal region, resulting in poor long-term efficacy.
In 2015, autologous LSCs were approved by the European Union as a commercial stem cell product for treating patients with chemically induced LSCD. However, LSCD patients are often accompanied by damage to the corneal stroma; while LSC transplantation can restore the limbal region and corneal epithelium, it cannot repair stromal opacities. Research indicates that transplantation of corneal stromal stem cells can reconstruct organized collagen structures and restore stromal transparency. Over the past decade, clinical studies using LSCs and corneal stromal stem cells to treat LSCD patients have been conducted in multiple countries, demonstrating the safety and efficacy of these stem cell therapies for corneal blindness.
Based on these findings above, the investigators have established a serum-free, carrier-free culture system that enables efficient and uniform in vitro expansion of functional LSCs and corneal stromal stem cells. By obtaining a 2 x 5 mm limbal tissue sample from the healthy eye of the patient, the investigators can acquire a sufficient number of cells for transplantation. Preclinical studies have confirmed that the expanded cells are effective and safe for treating LSCD animal models. This study aims to use autologous LSCs combined with corneal stromal stem cell transplantation to treat patients with unilateral LSCD, restoring their corneal transparency and visual function. This approach provides a novel treatment method for patients and promotes the application of stem cell regenerative medicine for the treatment of corneal blindness in China.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Chemical injury from acid or alkali exposure
- •Extensive limbal stem cell deficiency (greater than 180 degrees), with corneal stromal opacity not exceeding a depth of 250 μm
- •Corneal epithelial conjunctivalization and fibrosis, with neovascularization extending into more than half of the quadrants
- •Unilateral ocular involvement, with normal limbal stem cell function in the contralateral healthy eye
- •No significant improvement in ocular surface signs and symptoms after pharmacological or surgical interventions, stable for over three months
排除标准
- •Bilateral corneal stem cell deficiency, such as in Stevens-Johnson syndrome, ocular cicatricial pemphigoid, or congenital aniridia
- •Subclinical limbal stem cell deficiency in the contralateral eye
- •Signs of corneal endothelial decompensation, such as corneal bullae or corneal edema
- •Presence of infectious inflammation on the ocular surface
- •Severe dry eye
- •Eyelid abnormalities requiring corrective surgery to restore normal anatomical structure
- •Presence of chronic dacryocystitis, cataracts, uveitis, diabetic retinopathy, retinal detachment, or other ocular diseases
- •Patients who have undergone cataract surgery or other intraocular procedures
- •Glaucoma patients requiring long-term topical ocular medications
- •History of corneal perforation in the affected eye
- •Severe primary cardiovascular, hepatic, renal, endocrine, or hematologic disorders, diabetes, or immune deficiency in the medical history
- •Pregnant or lactating women
- •Positive screening for infectious diseases (HIV, HBV, HTLV, EBV, CMV, or syphilis)
- •Other vision-impairing diseases present
- •Allergy to bovine serum products
- •History of multiple drug allergies or hypersensitive constitution
- •Concurrent participation in other drug clinical trials
- •History of mental health disorders affecting the ability to comply with study requirements
- •Judged unsuitable for participation by the investigator
研究组 & 干预措施
Cornea limbal stem cell transplantation group
The corneal limbal tissue (2mm x 5mm) was harvested from the patient's healthy eye, and ex vivo amplification was performed to obtain an adequate quantity of transplantable corneal limbal stem cells The patient was followed up and re-examined for 2 years postoperatively.
干预措施: Cornea limbal stem cell transplantation group (Biological)
Cornea limbal stem cell transplantation combined corneal stromal stem cell group
The corneal limbal tissue (2mm x 5mm) was harvested from the patient's healthy eye, and ex vivo amplification was performed to obtain an adequate quantity of transplantable corneal limbal stem cells and corneal stromal stem cells. The patient was followed up and re-examined for 2 years postoperatively.
干预措施: Cornea limbal stem cell transplantation combined corneal stromal stem cell group (Biological)
Corneal transplantation group
The patient awaited allogeneic corneal donation and underwent corneal transplantation surgery. Postoperatively, the patient was followed up and re-examined for 2 years.
干预措施: Corneal transplantation (Procedure)
结局指标
主要结局
Vision
时间窗: [set the tissue sampling date at the begin] Enrollment, before the transplantation, First follow-up (Day 32), Second follow-up (Day 48), Third follow-up (Day 108), Fourth follow-up (6 months), Fifth follow-up (1 year), Sixth follow-up (2 years)
The patient should initially be positioned 5 meters from the visual acuity chart in a well-lit environment. Each eye is tested separately (the non-tested eye should be completely covered with an eye patch without applying pressure on the eyeball). During the test, the patient first views the largest line on the chart. If they can identify it, they proceed from top to bottom, viewing progressively smaller lines until the smallest identifiable line is determined. The patient should not spend more than 5 seconds reading each character.
次要结局
- Efficacy Scoring([set the corneal limbal tissue sampling date at the begin] First follow-up (Day 32), Second follow-up (Day 48), Third follow-up (Day 108), Fourth follow-up (6 months), Fifth follow-up (1 year), Sixth follow-up (2 years))
- Ocular adverse event evaluation([set the corneal limbal tissue sampling date at the begin] before the transplantation, First follow-up (Day 32), Second follow-up (Day 48), Third follow-up (Day 108), Fourth follow-up (6 months), Fifth follow-up (1 year), Sixth follow-up (2 years))
- ophthalmic examination（slit-lamp）([set the tissue sampling date at the begin] Enrollment, before the transplantation, First follow-up (Day 32), Second follow-up (Day 48), Third follow-up (Day 108), Fourth follow-up (6 months), Fifth follow-up (1 year), Sixth follow-up (2 years))
- cornea confocal([set the tissue sampling date at the begin] Enrollment, before the transplantation, Second follow-up (Day 48), Third follow-up (Day 108), Fourth follow-up (6 months), Fifth follow-up (1 year), Sixth follow-up (2 years))
- corneal topography([set the tissue sampling date at the begin] Enrollment, before the transplantation, First follow-up (Day 32), Second follow-up (Day 48), Third follow-up (Day 108), Fourth follow-up (6 months), Fifth follow-up (1 year), Sixth follow-up (2 years))
- Optical Coherence Tomography([set the tissue sampling date at the begin] Enrollment, before the transplantation, First follow-up (Day 32), Second follow-up (Day 48), Third follow-up (Day 108), Fourth follow-up (6 months), Fifth follow-up (1 year), Sixth follow-up (2 years))
- anterior segment photography([set the tissue sampling date at the begin] Enrollment, before the transplantation, First follow-up (Day 32), Second follow-up (Day 48), Third follow-up (Day 108), Fourth follow-up (6 months), Fifth follow-up (1 year), Sixth follow-up (2 years))
- VFQ-25 questionnaire([set the tissue sampling date at the begin] Enrollment, before the transplantation, Second follow-up (Day 48), Third follow-up (Day 108), Fourth follow-up (6 months), Fifth follow-up (1 year), Sixth follow-up (2 years))