Ocular instillation of conditioned medium from mesenchymal stem cells is effective for dry eye syndrome by improving corneal barrier function
Abstract Dry eye syndrome (DES) is a chronic ocular disease that induces epithelial damage to the cornea by decreasing tear production and quality. Adequate treatment options have not been established for severe DES such as Sjogren’s syndrome due to complicated pathological conditions. To solve this...
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Nature Portfolio
2023-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-40136-2 |
| _version_ | 1797453222190776320 |
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| author | Tsutomu Imaizumi Ryuhei Hayashi Yuji Kudo Xiaoqin Li Kaito Yamaguchi Shun Shibata Toru Okubo Tsuyoshi Ishii Yoichi Honma Kohji Nishida |
| author_facet | Tsutomu Imaizumi Ryuhei Hayashi Yuji Kudo Xiaoqin Li Kaito Yamaguchi Shun Shibata Toru Okubo Tsuyoshi Ishii Yoichi Honma Kohji Nishida |
| author_sort | Tsutomu Imaizumi |
| collection | DOAJ |
| description | Abstract Dry eye syndrome (DES) is a chronic ocular disease that induces epithelial damage to the cornea by decreasing tear production and quality. Adequate treatment options have not been established for severe DES such as Sjogren’s syndrome due to complicated pathological conditions. To solve this problem, we focused on the conditioned medium of human adipose-derived mesenchymal stem cells (hAdMSC-CM), which have multiple therapeutic properties. Here, we showed that hAdMSC-CM suppressed Benzalkonium Chloride (BAC)-induced cytotoxicity and inflammation in human corneal epithelial cells (hCECs). In addition, hAdMSC-CM increased the expression level and regulated the localisation of barrier function-related components, and improved the BAC-induced barrier dysfunction in hCECs. RNA-seq analysis and pharmacological inhibition experiments revealed that the effects of hAdMSC-CM were associated with the TGFβ and JAK-STAT signalling pathways. Moreover, in DES model rats with exorbital and intraorbital lacrimal gland excision, ocular instillation of hAdMSC-CM suppressed corneal epithelial damage by improving barrier dysfunction of the cornea. Thus, we demonstrated that hAdMSC-CM has multiple therapeutic properties associated with TGFβ and JAK-STAT signalling pathways, and ocular instillation of hAdMSC-CM may serve as an innovative therapeutic agent for DES by improving corneal barrier function. |
| first_indexed | 2024-03-09T15:19:40Z |
| format | Article |
| id | doaj.art-8c8b39604a854bff9cdcdd92184c8e66 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T15:19:40Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-8c8b39604a854bff9cdcdd92184c8e662023-11-26T12:55:05ZengNature PortfolioScientific Reports2045-23222023-08-0113111310.1038/s41598-023-40136-2Ocular instillation of conditioned medium from mesenchymal stem cells is effective for dry eye syndrome by improving corneal barrier functionTsutomu Imaizumi0Ryuhei Hayashi1Yuji Kudo2Xiaoqin Li3Kaito Yamaguchi4Shun Shibata5Toru Okubo6Tsuyoshi Ishii7Yoichi Honma8Kohji Nishida9Department of Stem Cells and Applied Medicine, Osaka University Graduate School of MedicineDepartment of Stem Cells and Applied Medicine, Osaka University Graduate School of MedicineDepartment of Stem Cells and Applied Medicine, Osaka University Graduate School of MedicineDepartment of Stem Cells and Applied Medicine, Osaka University Graduate School of MedicineDepartment of Stem Cells and Applied Medicine, Osaka University Graduate School of MedicineDepartment of Stem Cells and Applied Medicine, Osaka University Graduate School of MedicineDepartment of Stem Cells and Applied Medicine, Osaka University Graduate School of MedicineBasic Research Development Division, ROHTO PharmaceuticalBasic Research Development Division, ROHTO PharmaceuticalDepartment of Ophthalmology, Osaka University Graduate School of MedicineAbstract Dry eye syndrome (DES) is a chronic ocular disease that induces epithelial damage to the cornea by decreasing tear production and quality. Adequate treatment options have not been established for severe DES such as Sjogren’s syndrome due to complicated pathological conditions. To solve this problem, we focused on the conditioned medium of human adipose-derived mesenchymal stem cells (hAdMSC-CM), which have multiple therapeutic properties. Here, we showed that hAdMSC-CM suppressed Benzalkonium Chloride (BAC)-induced cytotoxicity and inflammation in human corneal epithelial cells (hCECs). In addition, hAdMSC-CM increased the expression level and regulated the localisation of barrier function-related components, and improved the BAC-induced barrier dysfunction in hCECs. RNA-seq analysis and pharmacological inhibition experiments revealed that the effects of hAdMSC-CM were associated with the TGFβ and JAK-STAT signalling pathways. Moreover, in DES model rats with exorbital and intraorbital lacrimal gland excision, ocular instillation of hAdMSC-CM suppressed corneal epithelial damage by improving barrier dysfunction of the cornea. Thus, we demonstrated that hAdMSC-CM has multiple therapeutic properties associated with TGFβ and JAK-STAT signalling pathways, and ocular instillation of hAdMSC-CM may serve as an innovative therapeutic agent for DES by improving corneal barrier function.https://doi.org/10.1038/s41598-023-40136-2 |
| spellingShingle | Tsutomu Imaizumi Ryuhei Hayashi Yuji Kudo Xiaoqin Li Kaito Yamaguchi Shun Shibata Toru Okubo Tsuyoshi Ishii Yoichi Honma Kohji Nishida Ocular instillation of conditioned medium from mesenchymal stem cells is effective for dry eye syndrome by improving corneal barrier function Scientific Reports |
| title | Ocular instillation of conditioned medium from mesenchymal stem cells is effective for dry eye syndrome by improving corneal barrier function |
| title_full | Ocular instillation of conditioned medium from mesenchymal stem cells is effective for dry eye syndrome by improving corneal barrier function |
| title_fullStr | Ocular instillation of conditioned medium from mesenchymal stem cells is effective for dry eye syndrome by improving corneal barrier function |
| title_full_unstemmed | Ocular instillation of conditioned medium from mesenchymal stem cells is effective for dry eye syndrome by improving corneal barrier function |
| title_short | Ocular instillation of conditioned medium from mesenchymal stem cells is effective for dry eye syndrome by improving corneal barrier function |
| title_sort | ocular instillation of conditioned medium from mesenchymal stem cells is effective for dry eye syndrome by improving corneal barrier function |
| url | https://doi.org/10.1038/s41598-023-40136-2 |
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