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...

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Main Authors: Seungwon An, Xiang Shen, Khandaker Anwar, Mohammadjavad Ashraf, Hyungjo Lee, Raghuram Koganti, Mahmood Ghassemi, Ali R. Djalilian
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
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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.
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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
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