the Treatment of Human Bone Marrow Mesenchymal Stem Cells in Ocular Corneal Burn

The Subconjunctival Injection of Human Bone Marrow Mesenchymal Stem Cells for Ocular Corneal Burn: Prospective, Case Series Study

Ocular chemical burn is one of the cause of vision loss in our country, and there are no satisfactory treatment. Human bone marrow mesenchymal stem cells (MSC) have the biological characteristics of self-renewal, immune regulation, multidirectional differentiation and tissue repair. Our preliminary research showed that in corneal alkali injury rats, the MSC can accelerated the cornea repair, inhibited angiogenesis. The aim of this study is to access the efficacy and safety of mesenchymal stem cell in the treatment of corneal burn in human.

Study Overview

• Status: Completed
• Conditions: Chemical Burns
• Intervention / Treatment: Other: human bone marrow MSC

Detailed Description

Corneal burn is a ocular damage disease included chemically burned and thermally burned. Surgery of corneal transplantation，amniotic membrane transplantation are some of effective,however,these therapy are expensive and the transplantation resources are limited. To arrest the inflammatory phase, several types of immunosuppressive treatments have been investigated. Corticosteroids also is important, however, long time usage of corticosteroids often cause severe side-effects. Human bone marrow mesenchymal stem cells (MSC) have the biological characteristics of self -renewal, immune regulation, multidirectional differentiation and tissue repair. Our preliminary research showed that in corneal alkali injury rats, the MSC can accelerated the cornea repair, inhibited angiogenesis. Many animal research also revealed that MSC have effect on the ocular alkali burned. And subconjunctivity injection is efficient, the clinical study of MSC on treating other disease have been developed rapidly recently, in further ,the outcome are encouraging, and no side-effect related MSC was reported, MSC can come from bone marrow, Umbilical cord blood，Adipose tissue and so on, but bone marrow MSC is mostly common used. The investigators propose to assess the efficacy and safety of human bone marrow mesenchymal stem cell in the treatment of corneal burn in human.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. must be ocular burns including chemically burned or the thermally burned
2. the severity degree should above the Ⅳ degree,including the Ⅳ degree(according the classification of Dua standard,2001)
3. the subjects are willing to accept this research,and promise to coordinate with the researchers during the follow up period
4. the subjects should abide by the laws and rules of the study.
5. the incident time should be within 2 weeks -

Exclusion Criteria:

1. the visual acuity is blind in any of the eye
2. have corneal perforation or have the corneal perforation tendency
3. have been accepted surgury on eyeball after trauma
4. IOP≥25mmHg even after antiglaucoma
5. have the history of other corneal diseaze or surgury
6. have the history of radiotherapy or surgury in the eyeball
7. associated with corneal ulcer or endoophthalmitis
8. uncontrolled hypertension(≥150/95mmHg)
9. abnormal liver and renal function
10. the pregancy women -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: human bone marrow MSC; 5×106/0.5ml MSC was injected subconjunctival at the inferior fornix.If persistent epithelial defect was noted thereafter, a second AMT and MSC injection was performed.	Other: human bone marrow MSC; The arms of active comparator :human bone marrow MSC subconjunctival injection once time. If persistent epithelial defect was noted thereafter, a second MSC injection was performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events by subconjunctival injection of BMMSCs	Record the adverse events, including topical complications such as ocular infection, conjunctival necrosis at the injection site, retinal artery occlusion, and systemic complications such as fever, urticaria, hemolysis, hypotension, renal and liver dysfunction, tumor formation, and/or abnormalities in complete blood counts.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of corneal perforation rate after subconjunctival injection of BMMSCs	the number of corneal perforation eyes/total eyes	6 months
Time of corneal epithelialization	record the time when cornea finish epithelialization	6 month
Visual acuity	Use the visual chart to record the decimal visual acuity	6 month

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Study Chair: Liang Dan, MD, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China

Publications and helpful links

General Publications

• Le Blanc K, Mougiakakos D. Multipotent mesenchymal stromal cells and the innate immune system. Nat Rev Immunol. 2012 Apr 25;12(5):383-96. doi: 10.1038/nri3209.
• Gao XH, Roberts A. The left triangular ligament of the liver and the structures in its free edge (appendix fibrosa hepatis) in Chinese and Canadian cadavers. Am Surg. 1986 May;52(5):246-52.
• Hargraves MM. Discovery of the LE cell and its morphology. Mayo Clin Proc. 1969 Sep;44(9):579-99. No abstract available.

Helpful Links

• Multipotent mesenchymal stromal cells and the innate immune system
• Immunoregulatory properties of clinical grade mesenchymal stromal cells: evidence, uncertainties, and clinical application
• Modulation of the Early Inflammatory Microenvironment in the Alkali-Burned Eye by Systemically Administered Interferon-gamma-Treated Mesenchymal Stromal Cells

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: December 10, 2014
• First Submitted That Met QC Criteria: December 20, 2014
• First Posted (Estimate): December 25, 2014

Study Record Updates

• Last Update Posted (Actual): April 11, 2019
• Last Update Submitted That Met QC Criteria: April 9, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Burns; Burns, Chemical
• Other Study ID Numbers: 2014MEKY059