Mesenchymal Stromal Cell Therapy for Corneal Ulcers

Recruiting at 3 trial locations

Overseen By Charlotte E Joslin, OD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Illinois at Chicago

Disqualifiers: Active ocular infection, Ocular surgery, Uncontrolled diabetes, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

38 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment using mesenchymal stromal cells, special cells from bone marrow, to heal stubborn corneal ulcers—painful open sores on the eye that haven't improved with standard treatments. The trial aims to determine if these cells can effectively repair the eye's surface. Participants will receive either the cell therapy or a placebo, allowing researchers to compare outcomes. Individuals with corneal ulcers that haven't healed after at least two weeks of other treatments might be suitable candidates. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not have any ocular drug toxicity less than two weeks ago and should not use any investigational agent within four weeks of the screening visit.

Is there any evidence suggesting that Mesenchymal Stromal Cell therapy is likely to be safe for humans?

Research has shown that the type of cells used in this study, called mesenchymal stromal cells (MSCs), are generally safe and well-tolerated. These cells are unlikely to trigger an immune response, so they won't cause the body to react negatively. In previous studies, MSCs effectively healed eye injuries in animals, demonstrating their potential without major safety issues. Additionally, their use in earlier studies supports their safety for humans. This suggests that the MSC therapy in this trial is expected to be safe for participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for corneal ulcers, which often involve antibiotics or corticosteroids, Mesenchymal Stromal Cell (MSC) therapy offers a novel approach by utilizing cells that can promote healing and reduce inflammation. Researchers are excited about MSC therapy because these cells have the ability to regenerate damaged tissue and modulate the immune response, potentially leading to faster and more effective healing. Additionally, the delivery method of subconjunctival injection directly targets the affected area, which could enhance the treatment's effectiveness compared to traditional topical or oral medications. This innovative approach represents a promising advancement in treating corneal ulcers that could significantly improve patient outcomes.

What evidence suggests that Mesenchymal Stromal Cell therapy could be effective for corneal ulcers?

Research has shown that mesenchymal stromal cells (MSCs) can aid in healing wounds, including those on the eye's surface. These cells remove certain immune cells that can impede healing. In this trial, participants will receive either a medium dose of allogenic MSC drops or a control treatment. Studies have also demonstrated that MSCs are safe in many trials. They quickly respond to signals in the body to initiate the healing process. MSCs are considered a powerful tool in regenerative medicine, which aims to repair or replace damaged cells or tissues. ^{6 7 8 9 10}

Who Is on the Research Team?

Ali R Djalilian, MD

Principal Investigator

University of Illinois at Chicago

Charlotte E Joslin, OD, PhD

Principal Investigator

University of Illinois at Chicago

Are You a Good Fit for This Trial?

This trial is for patients with persistent corneal ulcers not improving over the last 2 weeks, despite standard treatments. They must have a certain level of visual acuity and be able to follow study procedures. Excluded are those with recent ocular drug toxicity, prior specific eye surgeries (except amniotic membrane transplantation under conditions), anticipated need for punctual occlusion, severe corneal damage, systemic diseases affecting study outcomes, current use of investigational agents or participation in other studies.

Inclusion Criteria

My eye condition hasn't improved after 2 weeks of standard treatment.

My eye condition affects less than 80% of my cornea's diameter.

Visual Acuity: Best corrected distance visual acuity (BCDVA) score ≤ 75 ETDRS letters, (≥ 0.2 LogMAR, ≤ 20/32 Snellen or ≤ 0.625 decimal fraction) in the affected eye

Exclusion Criteria

I have not had eye surgery in the last 3 months.

I have severe eye damage, including deep corneal ulceration or cornea melting.

I have an eyelid issue that prevents me from closing my eyes properly.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subconjunctival injections of allogeneic MSCs or control vehicle to assess efficacy on corneal repair

12 weeks

Visits on Days 1-7, 28, 60, 90

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mesenchymal Stromal Cells

Trial Overview

The trial tests the effectiveness of Mesenchymal Stromal Cells (MSCs) derived from bone marrow on chronic epitheliopathies. MSCs will be compared to a control solution to see if they can heal corneal ulcers better. The MSCs are administered through subconjunctival injection near the affected area.

How Is the Trial Designed?

Group I: Medium dose of allogenic MSC drops Active Control 1 Intervention

Dose of allogeneic MSC subconjunctival injection will be assigned 3,000,000 cells/150 µL.

Group II: Control Group Placebo Group 1 Intervention

For the control group, 50 µL of the freezing media (vehicle) will be injected.

Mesenchymal Stromal Cells is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Mesenchymal Stromal Cells for:

• Graft-versus-host disease (GVHD)
• Autoimmune diseases

Approved in United States as Mesenchymal Stromal Cells for:

• Graft-versus-host disease (GVHD)
• Pediatric steroid-refractory GVHD

Approved in Canada as Mesenchymal Stromal Cells for:

• Pediatric steroid-refractory GVHD

Approved in Japan as Mesenchymal Stromal Cells for:

• Pediatric steroid-refractory GVHD

Who Is Running the Clinical Trial?

University of Illinois at Chicago

Lead Sponsor

Trials

653

Recruited

1,574,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

Topical application of bone marrow (BM) cells and CD117-positive hematopoietic stem cells significantly accelerated the healing of alkali-induced corneal ulcers in a study involving 89 eyes of syngenic mice.

The positive effects on corneal wound healing were likely due to soluble factors released by the BM and CD117(+) cells, as these cells were not found integrated into the regenerated corneal epithelium.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone marrow cells and CD117-positive haematopoietic stem cells promote corneal wound healing. Sel, S., Schilling, UM., Nass, N., et al.[2013]

This study identified mesenchymal stem cells (MC-L) in the limbus of the human eye, which resemble bone marrow-derived mesenchymal stem cells (MSC-BM), indicating a potential role in ocular wound healing.

Both MC-L and MSC-BM demonstrated the ability to form colonies and differentiate into adipocytes and osteocytes, suggesting their multipotent nature and potential therapeutic applications in regenerative medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal cells from limbal stroma of human eye. Polisetty, N., Fatima, A., Madhira, SL., et al.[2021]

Corneal stromal stem cells, found beneath the limbal basement membrane, have characteristics of adult stem cells and can differentiate into various cell types, including keratocytes, making them valuable for research and bioengineering.

These stromal stem cells can also remodel damaged tissue, reduce inflammation, and restore transparency in the cornea, suggesting their potential for autologous treatments for corneal opacities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem Cells in the Limbal Stroma. Funderburgh, JL., Funderburgh, ML., Du, Y.[2018]

Corneal mesenchymal stem/stromal cells (cMSCs) can be successfully generated and expanded from human cadaveric corneas using an explant method, yielding approximately 12 to 16 billion cells by passage 5 (P5).

P5 cMSCs demonstrated significant therapeutic effects, promoting faster wound healing and reducing inflammation in mouse models of corneal injury, indicating their potential for clinical applications in treating corneal damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reproducible Derivation and Expansion of Corneal Mesenchymal Stromal Cells for Therapeutic Applications. Jabbehdari, S., Yazdanpanah, G., Kanu, LN., et al.[2021]

Bone marrow-derived and adipose tissue-derived mesenchymal stem cells (MSCs) both significantly improved corneal wound healing in Wistar rats, as evidenced by increased keratocyte density and expression of key proteins related to corneal health after 8 weeks.

Transplanted MSCs led to a reduction in inflammatory markers (TNF-α, IL-6R, IL-12b), suggesting that these stem cells not only promote healing but also help reduce inflammation in the cornea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of bone marrow and adipose tissue-derived mesenchymal stem cells on the natural course of corneal scarring after penetrating injury. Demirayak, B., Yüksel, N., Çelik, OS., et al.[2018]

Topical treatment with adipose-derived stem cells (ADSC) significantly improved corneal wound healing in injured rat corneas, showing smaller epithelial defects compared to control and adipose-treated eyes.

Histological analysis revealed that ADSC-treated corneas achieved complete re-epithelization with reduced inflammation and fibroblast activation, indicating a beneficial effect on corneal repair mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human adipose-derived stem cells for the treatment of chemically burned rat cornea: preliminary results. Zeppieri, M., Salvetat, ML., Beltrami, AP., et al.[2013]

MesenCult-XF medium was found to be the most effective method for culturing human limbal mesenchymal stromal cells (L-MSC), achieving over 95% purity of specific cell markers and demonstrating multipotency.

L-MSC cultured in MesenCult-XF supported the growth of human limbal epithelial cells, indicating their potential role in corneal tissue engineering and repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of methods for cultivating limbal mesenchymal stromal cells. Bray, LJ., Heazlewood, CF., Atkinson, K., et al.[2022]

Corneal stroma-derived stem cells (CSSCs) show promise in tissue engineering and regenerative medicine, with potential applications in cellular therapies due to their mesenchymal stem cell-like properties.

CSSCs can be easily isolated and cultivated from postmortem corneal tissue, making them a cost-effective and accessible source for research and clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation and Culture of Corneal Stromal Stem Cells. Nagymihaly, RM., Moe, MC., Petrovski, G.[2021]

After corneal injury in mice, there was a significant increase in circulating endogenous mesenchymal stem cells (MSCs) within 48 hours, indicating a natural response to injury.

Injected MSCs specifically targeted the injured cornea and promoted rapid epithelial regeneration, suggesting their potential as a therapeutic option for enhancing tissue repair in corneal injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kinetics and function of mesenchymal stem cells in corneal injury. Lan, Y., Kodati, S., Lee, HS., et al.[2018]

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