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

Trial Summary

What is the purpose of this trial?

The proposed Conventional Cohort Expansion Study involves the use of Mesenchymal Stromal Cells (MSCs) are derived from the bone marrow. We previously studied the safety of subconjunctival injection of allogeneic bone marrow-derived MSCs in patients with nonhealing epitheliopathy (IRB Protocol 2020-0334). In the present study, we want to study the efficacy of this treatment on chronic epitheliopathies.

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.

What data supports the effectiveness of the treatment Mesenchymal Stromal Cells for corneal ulcers?

Research shows that mesenchymal stem cells, including those from bone marrow and adipose tissue, can help heal corneal injuries by reducing scarring and promoting tissue repair. These cells have been shown to successfully integrate into the cornea and improve healing outcomes in animal studies. ^{1 2 3 4 5}

Is Mesenchymal Stromal Cell Therapy generally safe for humans?

Research indicates that mesenchymal stromal cells, including those derived from adipose tissue and corneal stroma, are considered safe and non-immunogenic (do not trigger an immune response) in various applications. These cells have been shown to have the potential to suppress inflammation and support tissue regeneration, suggesting a favorable safety profile. ^{2 3 6 7 8}

How is Mesenchymal Stromal Cell Therapy different from other treatments for corneal ulcers?

Mesenchymal Stromal Cell Therapy is unique because it uses stem cells from the limbal stroma of the eye, which can transform into different cell types and help repair damaged tissue, reduce inflammation, and restore clarity to the cornea. This approach is different from traditional treatments as it focuses on regenerating the corneal tissue rather than just managing symptoms. ^{1 2 7 8 9}

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

Eligibility Criteria

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.

Study Procedures: Patients must have the ability and willingness to comply with study procedures

Exclusion Criteria

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

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

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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 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]

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]

References

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

Bone marrow cells and CD117-positive haematopoietic stem cells promote corneal wound healing. [2013]

2. England pubmed.ncbi.nlm.nih.gov

Evaluation of methods for cultivating limbal mesenchymal stromal cells. [2022]

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

Reproducible Derivation and Expansion of Corneal Mesenchymal Stromal Cells for Therapeutic Applications. [2021]

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

Kinetics and function of mesenchymal stem cells in corneal injury. [2018]

5. England 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. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Human adipose-derived stem cells for the treatment of chemically burned rat cornea: preliminary results. [2013]

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

Stem Cells in the Limbal Stroma. [2018]

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

Isolation and Culture of Corneal Stromal Stem Cells. [2021]

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

Mesenchymal cells from limbal stroma of human eye. [2021]