Therapeutic Potential of Mesenchymal Stem Cell-Secreted Factors on Delay in Corneal Wound Healing by Nitrogen Mustard
Ocular surface exposure to nitrogen mustard (NM) leads to severe ocular toxicity which includes the separation of epithelial and stromal layers, loss of endothelial cells, cell death, and severe loss of tissue function. No definitive treatment for mustard gas-induced ocular surface disorders is curr...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2022-09-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/23/19/11510 |
_version_ | 1797479006137745408 |
---|---|
author | Seungwon An Xiang Shen Khandaker Anwar Mohammadjavad Ashraf Hyungjo Lee Raghuram Koganti Mahmood Ghassemi Ali R. Djalilian |
author_facet | Seungwon An Xiang Shen Khandaker Anwar Mohammadjavad Ashraf Hyungjo Lee Raghuram Koganti Mahmood Ghassemi Ali R. Djalilian |
author_sort | Seungwon An |
collection | DOAJ |
description | Ocular surface exposure to nitrogen mustard (NM) leads to severe ocular toxicity which includes the separation of epithelial and stromal layers, loss of endothelial cells, cell death, and severe loss of tissue function. No definitive treatment for mustard gas-induced ocular surface disorders is currently available. The research was conducted to investigate the therapeutic potential of mesenchymal stem cell-conditioned media (MSC-CM) in NM-induced corneal wounds. NM was added to different types of corneal cells, the ocular surface of porcine, and the ocular surface of mice, followed by MSC-CM treatment. NM significantly induced apoptotic cell death, cellular ROS (Reactive oxygen species), and reduced cell viability, metabolic gene expression, and mitochondrial function, and, in turn, delayed wound healing. The application of MSC-CM post NM exposure partially restored mitochondrial function and decreased intracellular ROS generation which promoted cell survival. MSC-CM therapy enhanced wound healing process. MSC-CM inhibited NM-induced apoptotic cell death in murine and porcine corneal tissue. The application of MSC-CM following a chemical insult led to significant improvements in the preservation of corneal structure and wound healing. In vitro, ex vivo, and in vivo results suggest that MSC-CM can potentially provide targeted therapy for the treatment of chemical eye injuries, including mustard gas keratopathy (MGK) which presents with significant loss of vision alongside numerous corneal pathologies. |
first_indexed | 2024-03-09T21:39:43Z |
format | Article |
id | doaj.art-ecd05b34bce74d5586a67bf5b19c10cb |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-09T21:39:43Z |
publishDate | 2022-09-01 |
publisher | MDPI AG |
record_format | Article |
series | International Journal of Molecular Sciences |
spelling | doaj.art-ecd05b34bce74d5586a67bf5b19c10cb2023-11-23T20:34:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123191151010.3390/ijms231911510Therapeutic Potential of Mesenchymal Stem Cell-Secreted Factors on Delay in Corneal Wound Healing by Nitrogen MustardSeungwon An0Xiang Shen1Khandaker Anwar2Mohammadjavad Ashraf3Hyungjo Lee4Raghuram Koganti5Mahmood Ghassemi6Ali R. Djalilian7Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USADepartment of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USADepartment of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USADepartment of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USADepartment of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USADepartment of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USADepartment of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USADepartment of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USAOcular surface exposure to nitrogen mustard (NM) leads to severe ocular toxicity which includes the separation of epithelial and stromal layers, loss of endothelial cells, cell death, and severe loss of tissue function. No definitive treatment for mustard gas-induced ocular surface disorders is currently available. The research was conducted to investigate the therapeutic potential of mesenchymal stem cell-conditioned media (MSC-CM) in NM-induced corneal wounds. NM was added to different types of corneal cells, the ocular surface of porcine, and the ocular surface of mice, followed by MSC-CM treatment. NM significantly induced apoptotic cell death, cellular ROS (Reactive oxygen species), and reduced cell viability, metabolic gene expression, and mitochondrial function, and, in turn, delayed wound healing. The application of MSC-CM post NM exposure partially restored mitochondrial function and decreased intracellular ROS generation which promoted cell survival. MSC-CM therapy enhanced wound healing process. MSC-CM inhibited NM-induced apoptotic cell death in murine and porcine corneal tissue. The application of MSC-CM following a chemical insult led to significant improvements in the preservation of corneal structure and wound healing. In vitro, ex vivo, and in vivo results suggest that MSC-CM can potentially provide targeted therapy for the treatment of chemical eye injuries, including mustard gas keratopathy (MGK) which presents with significant loss of vision alongside numerous corneal pathologies.https://www.mdpi.com/1422-0067/23/19/11510nitrogen mustardmesenchymal stem cell-conditioned mediacorneal injuryapoptotic cell deathcellular ROSdelayed wound healing |
spellingShingle | Seungwon An Xiang Shen Khandaker Anwar Mohammadjavad Ashraf Hyungjo Lee Raghuram Koganti Mahmood Ghassemi Ali R. Djalilian Therapeutic Potential of Mesenchymal Stem Cell-Secreted Factors on Delay in Corneal Wound Healing by Nitrogen Mustard International Journal of Molecular Sciences nitrogen mustard mesenchymal stem cell-conditioned media corneal injury apoptotic cell death cellular ROS delayed wound healing |
title | Therapeutic Potential of Mesenchymal Stem Cell-Secreted Factors on Delay in Corneal Wound Healing by Nitrogen Mustard |
title_full | Therapeutic Potential of Mesenchymal Stem Cell-Secreted Factors on Delay in Corneal Wound Healing by Nitrogen Mustard |
title_fullStr | Therapeutic Potential of Mesenchymal Stem Cell-Secreted Factors on Delay in Corneal Wound Healing by Nitrogen Mustard |
title_full_unstemmed | Therapeutic Potential of Mesenchymal Stem Cell-Secreted Factors on Delay in Corneal Wound Healing by Nitrogen Mustard |
title_short | Therapeutic Potential of Mesenchymal Stem Cell-Secreted Factors on Delay in Corneal Wound Healing by Nitrogen Mustard |
title_sort | therapeutic potential of mesenchymal stem cell secreted factors on delay in corneal wound healing by nitrogen mustard |
topic | nitrogen mustard mesenchymal stem cell-conditioned media corneal injury apoptotic cell death cellular ROS delayed wound healing |
url | https://www.mdpi.com/1422-0067/23/19/11510 |
work_keys_str_mv | AT seungwonan therapeuticpotentialofmesenchymalstemcellsecretedfactorsondelayincornealwoundhealingbynitrogenmustard AT xiangshen therapeuticpotentialofmesenchymalstemcellsecretedfactorsondelayincornealwoundhealingbynitrogenmustard AT khandakeranwar therapeuticpotentialofmesenchymalstemcellsecretedfactorsondelayincornealwoundhealingbynitrogenmustard AT mohammadjavadashraf therapeuticpotentialofmesenchymalstemcellsecretedfactorsondelayincornealwoundhealingbynitrogenmustard AT hyungjolee therapeuticpotentialofmesenchymalstemcellsecretedfactorsondelayincornealwoundhealingbynitrogenmustard AT raghuramkoganti therapeuticpotentialofmesenchymalstemcellsecretedfactorsondelayincornealwoundhealingbynitrogenmustard AT mahmoodghassemi therapeuticpotentialofmesenchymalstemcellsecretedfactorsondelayincornealwoundhealingbynitrogenmustard AT alirdjalilian therapeuticpotentialofmesenchymalstemcellsecretedfactorsondelayincornealwoundhealingbynitrogenmustard |