Stem Cell Transplant for Limbal Stem Cell Deficiency

Overseen By Sheyla Gonzalez, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, Los Angeles

Disqualifiers: Pregnant, Diabetes, Ocular tumor, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 12 months

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with Limbal Stem Cell Deficiency (LSCD), a condition affecting the eye's surface that can lead to vision problems. The treatment uses cultivated limbal stem cells (cLSC) to repair the damaged cornea. Participants may receive either the stem cell treatment or a special contact lens designed to stabilize and improve the eye's surface. This trial suits those diagnosed with LSCD, who have significant vision impairment in one eye, and have not found success with other surgeries in the past six months. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that treatments using cultivated limbal stem cells (cLSC) are likely safe. Studies have found that umbilical cord blood stem cells, similar to cLSC, are generally safe for people. These cells are rarely contaminated by viruses and pose little risk to donors. Other similar cell-based treatments have been studied to reduce the need for strong immune system drugs after transplants.

As a Phase 1 study, the primary focus is on safety. Phase 1 trials typically test treatments on a small group to gather safety information. This phase is crucial to ensure the treatment is well-tolerated. While specific data on cLSC is limited, existing research and the nature of Phase 1 studies suggest that the treatment is expected to be safe for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for limbal stem cell deficiency, which typically involve strategies like corneal transplants or artificial tears, cultivated limbal stem-cells (cLSC) offer a regenerative approach. cLSC is unique because it uses living stem cells cultivated specifically to repair and regenerate damaged eye tissue, potentially leading to more durable and natural restoration of vision. Researchers are excited about cLSC because it targets the root cause of the deficiency by replenishing the limbal stem cells, which are critical for maintaining a healthy corneal surface. This innovative method could significantly improve outcomes for patients, offering a promising alternative to existing treatments.

What evidence suggests that this trial's treatments could be effective for Limbal Stem Cell Deficiency?

Research has shown that cultivated limbal stem cells (cLSC), a treatment under study in this trial, could help treat limbal stem cell deficiency. Studies on treatments using these cells have found that they can repair the eye's surface, improving vision and reducing the need for long-term medication. Animal studies support this, demonstrating that these stem cells can aid healing and reduce inflammation. Although more research on humans is necessary, early results suggest that cLSC might effectively restore damaged eye tissue in patients with this condition. ^{2 3 5 6 7}

Who Is on the Research Team?

Sophie Deng, MD, PhD

Principal Investigator

Stein Eye Institute UCLA

Are You a Good Fit for This Trial?

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

Have a life expectancy ≥ 2 years after enrollment

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

My eyelids close completely without any abnormalities.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• cLSC
• Scleral Contact Lens

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.

How Is the Trial Designed?

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.

cLSC is already approved in United States, European Union for the following indications:

Approved in United States as CLSCs for:

• Limbal Stem Cell Deficiency
• Corneal Wounds
• Diabetic Ulcers

Approved in European Union as Umbilical Cord Lining Stem Cells for:

• Limbal Stem Cell Deficiency
• Corneal Regeneration
• Wound Healing

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

California Institute for Regenerative Medicine (CIRM)

Collaborator

Trials

70

Recruited

3,300+

National Eye Institute (NEI)

Collaborator

Trials

572

Recruited

1,320,000+

Published Research Related to This Trial

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]

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]

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) has become a valuable alternative source of stem cells for transplantation, especially for patients without a matched donor, with over 2,500 transplants performed since 1998, primarily in children.

UCB transplants have a lower incidence of graft versus host disease due to the 'naive' nature of UCB lymphocytes, but they face challenges like lower stem cell yield, leading to higher graft failure rates and slower engraftment compared to traditional bone marrow transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cord blood biology and transplantation. Cohen, Y., Nagler, A.[2017]

Cord blood is a highly advantageous source of hematopoietic stem cells for transplants, offering benefits such as easier availability, shorter waiting times, and a lower incidence of graft-versus-host disease compared to bone marrow.

Over 200 cord blood transplants have been successfully performed for various conditions, and while traditionally used for pediatric patients, advancements in harvesting techniques are allowing for its use in adult patients as well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

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]

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 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]

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 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]

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]

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 (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]

Umbilical cord blood (UCB) stem cell transplantation is a viable alternative for treating severe primary T-cell immunodeficiencies in children when a matched sibling donor is unavailable, showing consistent and stable immune reconstitution.

The study demonstrated rapid recovery of immune function with low rates of graft-versus-host disease (GvHD) and low viral transmission risk, making UCB a safe and effective option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Umbilical cord blood transplantation in severe T-cell immunodeficiency disorders: two-year experience. Knutsen, AP., Wall, DA.[2022]

A 20-month-old boy with acute leukemia successfully underwent umbilical cord blood transplantation, showing a unique pattern of hematological recovery, including slow white cell recovery despite G-CSF treatment, and achieving platelet transfusion independence by day +31.

Immunological recovery was characterized by early natural killer (NK) cell recovery by 6 weeks and progressive T cell recovery over 3 months, although the CD4/CD8 ratio remained low for 14 months, indicating a distinct reconstitution pattern following umbilical cord blood transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune and hematopoietic reconstitution after transplantation of cord blood progenitor cells: case report and review of the literature. Elhasid, R., Ben Arush, MW., Pollack, S., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5634865/

Short review on human umbilical cord lining epithelial cells ... This review is directed at describing the various advantages the umbilical cord lining-derived epithelial cells have over other promising stem cell types.

2. aes.amegroups.org aes.amegroups.org/article/view/7277/html

Cell-based therapies for limbal stem cell deficiency Multiple cell-based therapies have been studied as alternative treatments to improve success rates and minimize immunosuppressive regimens after allogeneic ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6529262/

Strategies for Reconstructing the Limbal Stem Cell Niche This review summarizes and assesses the clinical feasibility and efficacy of current and emerging approaches for reconstruction of the limbal niche.

4. withpower.com withpower.com/trial/phase-1-8-2020-add73

Stem Cell Transplant for Limbal Stem Cell Deficiency 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.

5. preprints.org preprints.org/manuscript/202306.2119/v1

Growth Characteristics and Efficacy of Umbilical Cord ... Animal studies have demonstrated the diverse roles and beneficial effects of MSCs in promoting wound healing, reducing inflammation caused by ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4691643/

Limbal Stem Cell Deficiency: Current Treatment Options and ... This review focuses on limbal epithelial stem cells and the pathophysiology of LSCD. State-of-the-art therapeutic management of LSCD is described, and new and ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1319453414000691

Stem cell-based therapy for treating limbal ... In contrast to the alternative stem cells described above, the safety and efficiency of oral mucosal epithelium based transplantation has been evaluated ...