NCT06700655

A Clinical Study on Co-transplantation of Autologous Limbal Stem Cells and Corneal Stromal Stem Cells to Repair Corneal Injury

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

• Status: Not Yet Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Zhongshan Ophthalmic Center, Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Limbal Stem Cells Deficiency

Interventions

Type	Name	Description
BIOLOGICAL	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.
PROCEDURE	Corneal transplantation	The patient awaited allogeneic corneal donation and underwent corneal transplantation surgery.
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.

Timeline

• Start date: 2024-12-01
• Primary completion: 2028-12-01
• Completion: 2029-03-01
• First posted: 2024-11-22
• Last updated: 2024-11-22