Impact of Exosomes Released by Different Corneal Cell Types on the Wound Healing Properties of Human Corneal Epithelial Cells

Corneal wound healing involves communication between the different cell types that constitute the three cellular layers of the cornea (epithelium, stroma and endothelium), a process ensured in part by a category of extracellular vesicles called exosomes. In the present study, we isolated exosomes re...

Full description

Bibliographic Details
Main Authors: Pascale Desjardins, Rébecca Berthiaume, Camille Couture, Gaëtan Le-Bel, Vincent Roy, François Gros-Louis, Véronique J. Moulin, Stéphanie Proulx, Sylvain Chemtob, Lucie Germain, Sylvain L. Guérin
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/20/12201
_version_ 1797431571244908544
author Pascale Desjardins
Rébecca Berthiaume
Camille Couture
Gaëtan Le-Bel
Vincent Roy
François Gros-Louis
Véronique J. Moulin
Stéphanie Proulx
Sylvain Chemtob
Lucie Germain
Sylvain L. Guérin
author_facet Pascale Desjardins
Rébecca Berthiaume
Camille Couture
Gaëtan Le-Bel
Vincent Roy
François Gros-Louis
Véronique J. Moulin
Stéphanie Proulx
Sylvain Chemtob
Lucie Germain
Sylvain L. Guérin
author_sort Pascale Desjardins
collection DOAJ
description Corneal wound healing involves communication between the different cell types that constitute the three cellular layers of the cornea (epithelium, stroma and endothelium), a process ensured in part by a category of extracellular vesicles called exosomes. In the present study, we isolated exosomes released by primary cultured human corneal epithelial cells (hCECs), corneal fibroblasts (hCFs) and corneal endothelial cells (hCEnCs) and determined whether they have wound healing characteristics of their own and to which point they modify the genetic and proteomic pattern of these cell types. Exosomes released by all three cell types significantly accelerated wound closure of scratch-wounded hCECs in vitro compared to controls (without exosomes). Profiling of activated kinases revealed that exosomes from human corneal cells caused the activation of signal transduction mediators that belong to the HSP27, STAT, β-catenin, GSK-3β and p38 pathways. Most of all, data from gene profiling analyses indicated that exosomes, irrespective of their cellular origin, alter a restricted subset of genes that are completely different between each targeted cell type (hCECs, hCFS, hCEnCs). Analysis of the genes specifically differentially regulated for a given cell-type in the microarray data using the Ingenuity Pathway Analysis (IPA) software revealed that the mean gene expression profile of hCECs cultured in the presence of exosomes would likely promote cell proliferation and migration whereas it would reduce differentiation when compared to control cells. Collectively, our findings represent a conceptual advance in understanding the mechanisms of corneal wound repair that may ultimately open new avenues for the development of novel therapeutic approaches to improve closure of corneal wounds.
first_indexed 2024-03-09T09:47:05Z
format Article
id doaj.art-99dbce568d9043bb818f8fb96b3711eb
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-09T09:47:05Z
publishDate 2022-10-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
spelling doaj.art-99dbce568d9043bb818f8fb96b3711eb2023-12-02T00:31:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123201220110.3390/ijms232012201Impact of Exosomes Released by Different Corneal Cell Types on the Wound Healing Properties of Human Corneal Epithelial CellsPascale Desjardins0Rébecca Berthiaume1Camille Couture2Gaëtan Le-Bel3Vincent Roy4François Gros-Louis5Véronique J. Moulin6Stéphanie Proulx7Sylvain Chemtob8Lucie Germain9Sylvain L. Guérin10Regenerative Medicine Division of the Centre de Recherche du CHU de Québec, Université Laval, Québec, QC G1J 1Z4, CanadaRegenerative Medicine Division of the Centre de Recherche du CHU de Québec, Université Laval, Québec, QC G1J 1Z4, CanadaRegenerative Medicine Division of the Centre de Recherche du CHU de Québec, Université Laval, Québec, QC G1J 1Z4, CanadaRegenerative Medicine Division of the Centre de Recherche du CHU de Québec, Université Laval, Québec, QC G1J 1Z4, CanadaRegenerative Medicine Division of the Centre de Recherche du CHU de Québec, Université Laval, Québec, QC G1J 1Z4, CanadaRegenerative Medicine Division of the Centre de Recherche du CHU de Québec, Université Laval, Québec, QC G1J 1Z4, CanadaRegenerative Medicine Division of the Centre de Recherche du CHU de Québec, Université Laval, Québec, QC G1J 1Z4, CanadaRegenerative Medicine Division of the Centre de Recherche du CHU de Québec, Université Laval, Québec, QC G1J 1Z4, CanadaDépartement d’Ophtalmologie, Faculté de Médecine, Université de Montréal, Montréal, QC H3T 1J4, CanadaRegenerative Medicine Division of the Centre de Recherche du CHU de Québec, Université Laval, Québec, QC G1J 1Z4, CanadaRegenerative Medicine Division of the Centre de Recherche du CHU de Québec, Université Laval, Québec, QC G1J 1Z4, CanadaCorneal wound healing involves communication between the different cell types that constitute the three cellular layers of the cornea (epithelium, stroma and endothelium), a process ensured in part by a category of extracellular vesicles called exosomes. In the present study, we isolated exosomes released by primary cultured human corneal epithelial cells (hCECs), corneal fibroblasts (hCFs) and corneal endothelial cells (hCEnCs) and determined whether they have wound healing characteristics of their own and to which point they modify the genetic and proteomic pattern of these cell types. Exosomes released by all three cell types significantly accelerated wound closure of scratch-wounded hCECs in vitro compared to controls (without exosomes). Profiling of activated kinases revealed that exosomes from human corneal cells caused the activation of signal transduction mediators that belong to the HSP27, STAT, β-catenin, GSK-3β and p38 pathways. Most of all, data from gene profiling analyses indicated that exosomes, irrespective of their cellular origin, alter a restricted subset of genes that are completely different between each targeted cell type (hCECs, hCFS, hCEnCs). Analysis of the genes specifically differentially regulated for a given cell-type in the microarray data using the Ingenuity Pathway Analysis (IPA) software revealed that the mean gene expression profile of hCECs cultured in the presence of exosomes would likely promote cell proliferation and migration whereas it would reduce differentiation when compared to control cells. Collectively, our findings represent a conceptual advance in understanding the mechanisms of corneal wound repair that may ultimately open new avenues for the development of novel therapeutic approaches to improve closure of corneal wounds.https://www.mdpi.com/1422-0067/23/20/12201corneawound healingexosomesextracellular vesiclescorneal epithelial cellscorneal stromal fibroblasts
spellingShingle Pascale Desjardins
Rébecca Berthiaume
Camille Couture
Gaëtan Le-Bel
Vincent Roy
François Gros-Louis
Véronique J. Moulin
Stéphanie Proulx
Sylvain Chemtob
Lucie Germain
Sylvain L. Guérin
Impact of Exosomes Released by Different Corneal Cell Types on the Wound Healing Properties of Human Corneal Epithelial Cells
International Journal of Molecular Sciences
cornea
wound healing
exosomes
extracellular vesicles
corneal epithelial cells
corneal stromal fibroblasts
title Impact of Exosomes Released by Different Corneal Cell Types on the Wound Healing Properties of Human Corneal Epithelial Cells
title_full Impact of Exosomes Released by Different Corneal Cell Types on the Wound Healing Properties of Human Corneal Epithelial Cells
title_fullStr Impact of Exosomes Released by Different Corneal Cell Types on the Wound Healing Properties of Human Corneal Epithelial Cells
title_full_unstemmed Impact of Exosomes Released by Different Corneal Cell Types on the Wound Healing Properties of Human Corneal Epithelial Cells
title_short Impact of Exosomes Released by Different Corneal Cell Types on the Wound Healing Properties of Human Corneal Epithelial Cells
title_sort impact of exosomes released by different corneal cell types on the wound healing properties of human corneal epithelial cells
topic cornea
wound healing
exosomes
extracellular vesicles
corneal epithelial cells
corneal stromal fibroblasts
url https://www.mdpi.com/1422-0067/23/20/12201
work_keys_str_mv AT pascaledesjardins impactofexosomesreleasedbydifferentcornealcelltypesonthewoundhealingpropertiesofhumancornealepithelialcells
AT rebeccaberthiaume impactofexosomesreleasedbydifferentcornealcelltypesonthewoundhealingpropertiesofhumancornealepithelialcells
AT camillecouture impactofexosomesreleasedbydifferentcornealcelltypesonthewoundhealingpropertiesofhumancornealepithelialcells
AT gaetanlebel impactofexosomesreleasedbydifferentcornealcelltypesonthewoundhealingpropertiesofhumancornealepithelialcells
AT vincentroy impactofexosomesreleasedbydifferentcornealcelltypesonthewoundhealingpropertiesofhumancornealepithelialcells
AT francoisgroslouis impactofexosomesreleasedbydifferentcornealcelltypesonthewoundhealingpropertiesofhumancornealepithelialcells
AT veroniquejmoulin impactofexosomesreleasedbydifferentcornealcelltypesonthewoundhealingpropertiesofhumancornealepithelialcells
AT stephanieproulx impactofexosomesreleasedbydifferentcornealcelltypesonthewoundhealingpropertiesofhumancornealepithelialcells
AT sylvainchemtob impactofexosomesreleasedbydifferentcornealcelltypesonthewoundhealingpropertiesofhumancornealepithelialcells
AT luciegermain impactofexosomesreleasedbydifferentcornealcelltypesonthewoundhealingpropertiesofhumancornealepithelialcells
AT sylvainlguerin impactofexosomesreleasedbydifferentcornealcelltypesonthewoundhealingpropertiesofhumancornealepithelialcells