Stem Cell Transplant for Limbal Stem Cell Deficiency

Recruiting in Palo Alto (17 mi)

Overseen by Sophie Deng, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: University of California, Los Angeles

Disqualifiers: Pregnant, Diabetes, Ocular tumor, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment using lab-grown stem cells to repair severe eye damage in patients who have had injuries or surgeries. The goal is to see if these stem cells can safely and effectively help the eye heal. Stem cell therapy has been increasingly used for treating various diseases, including eye conditions, with limbal epithelial stem transplantation being the only eye-related cell therapy currently in clinical practice.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

What data supports the effectiveness of the treatment for Limbal Stem Cell Deficiency?

Research on umbilical cord blood (UCB) shows it is a valuable source of stem cells for various conditions, with benefits like rapid immune recovery and low risk of complications. While not directly related to Limbal Stem Cell Deficiency, these findings suggest potential benefits of using umbilical cord-derived stem cells in regenerative treatments. ^{1 2 3 4 5}

Is the use of umbilical cord blood stem cells generally safe for humans?

Umbilical cord blood stem cells are considered safe for use in humans, as they are rarely contaminated by viruses, pose no risk to the donor, and have a low incidence of graft-versus-host disease (a condition where transplanted cells attack the recipient's body). ^{6 7 8 9 10}

How is the treatment cLSC different from other treatments for limbal stem cell deficiency?

The treatment cLSC (Cord Lining Stem Cells) is unique because it uses stem cells derived from the umbilical cord lining, which is a novel source compared to traditional treatments that often use limbal stem cells from the patient's own eye or donor tissue. This approach may offer a new avenue for treating limbal stem cell deficiency, especially when other sources of stem cells are not available or suitable. ^{11 12 13 14 15}

Research Team

Sophie Deng, MD, PhD

Principal Investigator

Stein Eye Institute UCLA

Eligibility Criteria

This trial is for adults over 18 with Limbal Stem Cell Deficiency (LSCD) that hasn't improved after surgery in the last 6 months. Participants must have a vision of 20/200 or worse, diagnosed LSCD affecting the central cornea, no eyelid issues, and adequate eye moisture. Not eligible if pregnant, breastfeeding without birth control use during study, had chemical injury within last year, allergic to cLSC components, in another trial currently or have uncontrolled diabetes.

Inclusion Criteria

I am 18 years old or older.

Have a life expectancy ≥ 2 years after enrollment

Best corrected visual acuity in the affected eye of 20/200 or less

Exclusion Criteria

Current participation in another simultaneous medical investigation or trial

Unable to be compliant with or complete the requirements of the study

My eye is affected by exposure or cannot fully close.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cultivated limbal stem-cells (cLSC) or scleral contact lens device (SCL) treatment

12 months

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Follow-up visits at 6 and 12 months

Treatment Details

Interventions

• cLSC (Stem Cell Therapy)
• Scleral Contact Lens (Device)

Trial Overview The study tests cLSC's ability to be manufactured and transplanted onto patients' corneas successfully at surgery time. It aims to see if these cells can populate the ocular surface effectively without causing serious adverse events.

Participant Groups

Group I: Cultivated Limbal Stem-Cells (cLSC) Experimental Treatment 1 Intervention

One dose of cultivated limbal stem-cells (cLSC), size between 7.6 to 15 mm in the average diameter.

Group II: Scleral Contact Lens Device (SCL) Active Control 1 Intervention

Scleral contact lens device (SCL) will be fitted to stabilize and improve ocular surface.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of California Los Angeles, CA

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1594

Patients Recruited

10,430,000+

California Institute for Regenerative Medicine (CIRM)

Collaborator

Trials

70

Patients Recruited

3,300+

National Eye Institute (NEI)

Collaborator

Trials

572

Patients Recruited

1,320,000+

Findings from Research

Umbilical cord blood (UCB) is a valuable source of hematopoietic stem and progenitor cells (HSPCs) for treating blood disorders, offering advantages like rapid donor availability and lower rates of graft-versus-host disease compared to traditional sources like bone marrow.

Despite its benefits, the limited number of HSPCs in a single UCB unit can lead to challenges such as delayed engraftment and increased risk of complications, prompting the development of strategies to enhance HSPC numbers and improve their integration into the recipient's bone marrow.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Progress and Preclinical Insights Into Umbilical Cord Blood Transplantation Improvement. Sun, Z., Yao, B., Xie, H., et al.[2022]

Hematopoietic stem and progenitor cells from umbilical cord blood have been successfully used in approximately 90 transplantations worldwide, demonstrating effective restoration of blood cell production, with a 90% yield of unrelated cord blood-derived stem cell preparations for banking.

The study found that cord blood samples have a significantly lower rate of cytomegalovirus (CMV) positivity (0.3%) compared to unrelated bone marrow donors (>40%), which may provide a safety advantage for cord blood transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematopoietic transplant potential of unrelated cord blood: critical issues. Kögler, G., Callejas, J., Hakenberg, P., et al.[2019]

Umbilical cord blood (UCB) is a valuable graft source for hematopoietic cell transplants due to its low immunogenicity and less stringent HLA matching requirements, making it accessible for patients without fully matched donors.

Despite its advantages, UCB transplants face challenges such as delayed engraftment and increased risks of graft failure and infections, which need to be addressed to maintain its viability as a transplant option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Umbilical cord blood: The promise and the uncertainty. Kindwall-Keller, TL., Ballen, KK.[2021]

Umbilical cord blood (CB) has become an important source of hematopoietic stem cells for transplantation, showing a lower incidence of graft-versus-host disease compared to traditional bone marrow transplants, even with HLA mismatches.

Despite its benefits, umbilical cord blood transplantation has challenges such as slower recovery of blood cell production and a higher risk of graft failure due to the lower number of stem cells available for infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Umbilical cord blood transplantation. Petropoulos, D., Chan, KW.[2019]

Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells that can treat over 80 diseases, including cancers and genetic disorders, with significant advantages such as ease of collection and low risk of complications.

Despite its potential, 97% of cord blood is discarded after birth, highlighting the need for better awareness and collection efforts to make these stem cells available for patients in need.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The rationale behind collecting umbilical cord blood. Zech, NH., Broer, N., Ribitsch, I., et al.[2021]

Umbilical cord blood is a promising source of hematopoietic stem cells that is safe to collect, poses no risk to the donor, and has a low incidence of graft-versus-host disease (GVHD) in recipients, making it a viable option for unrelated transplantation.

The large-scale collection and banking of umbilical cord blood stem cells could address donor shortages, particularly for underrepresented ethnic and racial groups, and may offer advantages over traditional bone marrow transplants, although further studies are needed to confirm its efficacy in larger patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic umbilical cord blood transplantation. Wagner, JE.[2019]

Cultivated limbal epithelial cell (CLEC) transplantation showed promising results in treating unilateral limbal stem cell deficiency (LSCD), with all five patients experiencing improved visual acuity after one year, ranging from counting fingers at 3 meters to 6/10 vision.

The procedure was generally safe, with only one case of temporary hemorrhage and some peripheral corneal vascularization observed, indicating that CLEC transplantation is an effective and viable treatment option for LSCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ocular Surface Reconstruction with Cultivated Limbal Epithelial Cells in Limbal Stem Cell Deficiency: One-year Follow-up Results]. Durak, İ., Selver, ÖB., Erdal, E., et al.[2020]

Limbal stem cell deficiency leads to serious eye issues, including the invasion of conjunctival cells onto the cornea and chronic inflammation, which can severely affect vision.

Current treatments for this condition include amniotic membrane transplantation and keratolimbal grafts, but future therapies may involve stem cell transplantation and tissue engineering for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular surface reconstruction in limbal stem cell deficiency. Gheorghe, A., Pop, M., Mrini, F., et al.[2018]

Transplantation of autologous limbal stem cells cultured on human amniotic membrane (HAM) is a safe and effective method for reconstructing the corneal surface in patients with unilateral total limbal stem cell deficiency (LSCD), achieving 100% success in ocular surface reconstruction.

In a study involving 8 patients with a mean follow-up of 19 months, there was significant improvement in best corrected visual acuity in 5 eyes, and all patients reported reduced vision impairment and pain, indicating the therapeutic efficacy of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful clinical implementation of corneal epithelial stem cell therapy for treatment of unilateral limbal stem cell deficiency. Kolli, S., Ahmad, S., Lako, M., et al.[2022]

In a study of 72 limbal transplantations (LT) performed on 61 patients, the overall success rate was 66.7%, with a significantly higher success rate of 81.0% for autografts compared to only 7.1% for allografts, highlighting the effectiveness of using a patient's own tissue.

LT is particularly effective for treating recurrent pterygium, achieving an 80.0% success rate, while cases involving immune-based disorders were more challenging, with only a 14.3% success rate, indicating the need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Limbal transplantation: multicenter retrospective case series analysis]. Torres, J., Fernández, I., Quadrado, MJ., et al.[2019]

Limbal Stem Cell Deficiency (LSCD) is a serious eye condition that leads to problems like conjunctivalization due to a lack of functioning limbal stem cells, and surgery is often required for severe cases.

The article reviews five key surgical methods for treating LSCD, including conjunctival limbal autograft (CLAU) and cultivated limbal stem cell transplantation (CLET), highlighting the variety of approaches available to restore ocular surface health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Research progress on limbal stem cell transplantation]. Wang, LY., Liang, QF.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Clinical Progress and Preclinical Insights Into Umbilical Cord Blood Transplantation Improvement. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Umbilical cord blood transplantation in severe T-cell immunodeficiency disorders: two-year experience. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Hematopoietic transplant potential of unrelated cord blood: critical issues. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Immune and hematopoietic reconstitution after transplantation of cord blood progenitor cells: case report and review of the literature. [2019]

5. Israel pubmed.ncbi.nlm.nih.gov

Cord blood biology and transplantation. [2017]

6. India pubmed.ncbi.nlm.nih.gov

Cord blood transplant: current and future issues. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Umbilical cord blood: The promise and the uncertainty. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Umbilical cord blood transplantation. [2019]

9. Turkey pubmed.ncbi.nlm.nih.gov

The rationale behind collecting umbilical cord blood. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Allogeneic umbilical cord blood transplantation. [2019]

11. Turkey pubmed.ncbi.nlm.nih.gov

[Ocular Surface Reconstruction with Cultivated Limbal Epithelial Cells in Limbal Stem Cell Deficiency: One-year Follow-up Results]. [2020]

12. Romania pubmed.ncbi.nlm.nih.gov

Ocular surface reconstruction in limbal stem cell deficiency. [2018]

13. England pubmed.ncbi.nlm.nih.gov

Successful clinical implementation of corneal epithelial stem cell therapy for treatment of unilateral limbal stem cell deficiency. [2022]

14. Spain pubmed.ncbi.nlm.nih.gov

[Limbal transplantation: multicenter retrospective case series analysis]. [2019]

15. China pubmed.ncbi.nlm.nih.gov

[Research progress on limbal stem cell transplantation]. [2020]