Mesenchymal Stem Cell Exosomes as Immunomodulatory Therapy for Corneal Scarring
Corneal scarring is a leading cause of worldwide blindness. Human mesenchymal stem cells (MSC) have been reported to promote corneal wound healing through secreted exosomes. This study investigated the wound healing and immunomodulatory effects of MSC-derived exosomes (MSC-exo) in corneal injury thr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/8/7456 |
| _version_ | 1797605106425790464 |
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| author | Hon Shing Ong Andri K. Riau Gary Hin-Fai Yam Nur Zahirah Binte M. Yusoff Evelina J. Y. Han Tze-Wei Goh Ruenn Chai Lai Sai Kiang Lim Jodhbir S. Mehta |
| author_facet | Hon Shing Ong Andri K. Riau Gary Hin-Fai Yam Nur Zahirah Binte M. Yusoff Evelina J. Y. Han Tze-Wei Goh Ruenn Chai Lai Sai Kiang Lim Jodhbir S. Mehta |
| author_sort | Hon Shing Ong |
| collection | DOAJ |
| description | Corneal scarring is a leading cause of worldwide blindness. Human mesenchymal stem cells (MSC) have been reported to promote corneal wound healing through secreted exosomes. This study investigated the wound healing and immunomodulatory effects of MSC-derived exosomes (MSC-exo) in corneal injury through an established rat model of corneal scarring. After induction of corneal scarring by irregular phototherapeutic keratectomy (irrPTK), MSC exosome preparations (MSC-exo) or PBS vehicle as controls were applied to the injured rat corneas for five days. The animals were assessed for corneal clarity using a validated slit-lamp haze grading score. Stromal haze intensity was quantified using in-vivo confocal microscopy imaging. Corneal vascularization, fibrosis, variations in macrophage phenotypes, and inflammatory cytokines were evaluated using immunohistochemistry techniques and enzyme-linked immunosorbent assays (ELISA) of the excised corneas. Compared to the PBS control group, MSC-exo treatment group had faster epithelial wound closure (0.041), lower corneal haze score (<i>p</i> = 0.002), and reduced haze intensity (<i>p</i> = 0.004) throughout the follow-up period. Attenuation of corneal vascularisation based on CD31 and LYVE-1 staining and reduced fibrosis as measured by fibronectin and collagen 3A1 staining was also observed in the MSC-exo group. MSC-exo treated corneas also displayed a regenerative immune phenotype characterized by a higher infiltration of CD163+, CD206+ M2 macrophages over CD80+, CD86+ M1 macrophages (<i>p</i> = 0.023), reduced levels of pro-inflammatory IL-1β, IL-8, and TNF-α, and increased levels of anti-inflammatory IL-10. In conclusion, topical MSC-exo could alleviate corneal insults by promoting wound closure and reducing scar development, possibly through anti-angiogenesis and immunomodulation towards a regenerative and anti-inflammatory phenotype. |
| first_indexed | 2024-03-11T04:56:27Z |
| format | Article |
| id | doaj.art-bb90742d043e415399d58ad9f66b591a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:56:27Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bb90742d043e415399d58ad9f66b591a2023-11-17T19:40:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01248745610.3390/ijms24087456Mesenchymal Stem Cell Exosomes as Immunomodulatory Therapy for Corneal ScarringHon Shing Ong0Andri K. Riau1Gary Hin-Fai Yam2Nur Zahirah Binte M. Yusoff3Evelina J. Y. Han4Tze-Wei Goh5Ruenn Chai Lai6Sai Kiang Lim7Jodhbir S. Mehta8Tissue Engineering and Cell Therapy Group, Singapore Eye Research Institute, Singapore 169856, SingaporeTissue Engineering and Cell Therapy Group, Singapore Eye Research Institute, Singapore 169856, SingaporeTissue Engineering and Cell Therapy Group, Singapore Eye Research Institute, Singapore 169856, SingaporeTissue Engineering and Cell Therapy Group, Singapore Eye Research Institute, Singapore 169856, SingaporeTissue Engineering and Cell Therapy Group, Singapore Eye Research Institute, Singapore 169856, SingaporeTissue Engineering and Cell Therapy Group, Singapore Eye Research Institute, Singapore 169856, SingaporeInstitute of Medical Biology & Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138648, SingaporeInstitute of Medical Biology & Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138648, SingaporeTissue Engineering and Cell Therapy Group, Singapore Eye Research Institute, Singapore 169856, SingaporeCorneal scarring is a leading cause of worldwide blindness. Human mesenchymal stem cells (MSC) have been reported to promote corneal wound healing through secreted exosomes. This study investigated the wound healing and immunomodulatory effects of MSC-derived exosomes (MSC-exo) in corneal injury through an established rat model of corneal scarring. After induction of corneal scarring by irregular phototherapeutic keratectomy (irrPTK), MSC exosome preparations (MSC-exo) or PBS vehicle as controls were applied to the injured rat corneas for five days. The animals were assessed for corneal clarity using a validated slit-lamp haze grading score. Stromal haze intensity was quantified using in-vivo confocal microscopy imaging. Corneal vascularization, fibrosis, variations in macrophage phenotypes, and inflammatory cytokines were evaluated using immunohistochemistry techniques and enzyme-linked immunosorbent assays (ELISA) of the excised corneas. Compared to the PBS control group, MSC-exo treatment group had faster epithelial wound closure (0.041), lower corneal haze score (<i>p</i> = 0.002), and reduced haze intensity (<i>p</i> = 0.004) throughout the follow-up period. Attenuation of corneal vascularisation based on CD31 and LYVE-1 staining and reduced fibrosis as measured by fibronectin and collagen 3A1 staining was also observed in the MSC-exo group. MSC-exo treated corneas also displayed a regenerative immune phenotype characterized by a higher infiltration of CD163+, CD206+ M2 macrophages over CD80+, CD86+ M1 macrophages (<i>p</i> = 0.023), reduced levels of pro-inflammatory IL-1β, IL-8, and TNF-α, and increased levels of anti-inflammatory IL-10. In conclusion, topical MSC-exo could alleviate corneal insults by promoting wound closure and reducing scar development, possibly through anti-angiogenesis and immunomodulation towards a regenerative and anti-inflammatory phenotype.https://www.mdpi.com/1422-0067/24/8/7456mesenchymal stem cellsexosomesextracellular vesiclescorneascarringwound healing |
| spellingShingle | Hon Shing Ong Andri K. Riau Gary Hin-Fai Yam Nur Zahirah Binte M. Yusoff Evelina J. Y. Han Tze-Wei Goh Ruenn Chai Lai Sai Kiang Lim Jodhbir S. Mehta Mesenchymal Stem Cell Exosomes as Immunomodulatory Therapy for Corneal Scarring International Journal of Molecular Sciences mesenchymal stem cells exosomes extracellular vesicles cornea scarring wound healing |
| title | Mesenchymal Stem Cell Exosomes as Immunomodulatory Therapy for Corneal Scarring |
| title_full | Mesenchymal Stem Cell Exosomes as Immunomodulatory Therapy for Corneal Scarring |
| title_fullStr | Mesenchymal Stem Cell Exosomes as Immunomodulatory Therapy for Corneal Scarring |
| title_full_unstemmed | Mesenchymal Stem Cell Exosomes as Immunomodulatory Therapy for Corneal Scarring |
| title_short | Mesenchymal Stem Cell Exosomes as Immunomodulatory Therapy for Corneal Scarring |
| title_sort | mesenchymal stem cell exosomes as immunomodulatory therapy for corneal scarring |
| topic | mesenchymal stem cells exosomes extracellular vesicles cornea scarring wound healing |
| url | https://www.mdpi.com/1422-0067/24/8/7456 |
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