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

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.

• Efficacy Scoring [Time frame: [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 [Time frame: [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） [Time frame: [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 [Time frame: [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 [Time frame: [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 [Time frame: [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 [Time frame: [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 [Time frame: [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)]