Spheroid assembly of mesenchymal stem cells enhances secretome-mediated corneal reinnervation and epithelial repair in a mouse model of experimental dry eye
Dry eye disease is a complex ocular surface disorder with multifactorial pathophysiology, including corneal epithelial damage, chronic inflammation, and corneal nerve dysfunction. Among these, impaired corneal innervation plays a particularly critical role, as it disrupts neurotrophic support and te...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2025-08-01
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| Series: | Journal of Tissue Engineering |
| Online Access: | https://doi.org/10.1177/20417314251363300 |
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| author | Shao-Wen Liu Meng-Yu Tsai Yang-Chun Shen Yi-Jen Hsueh Han Chiu Li-Wen Hsu Hung-Chi Chen Chieh-Cheng Huang |
| author_facet | Shao-Wen Liu Meng-Yu Tsai Yang-Chun Shen Yi-Jen Hsueh Han Chiu Li-Wen Hsu Hung-Chi Chen Chieh-Cheng Huang |
| author_sort | Shao-Wen Liu |
| collection | DOAJ |
| description | Dry eye disease is a complex ocular surface disorder with multifactorial pathophysiology, including corneal epithelial damage, chronic inflammation, and corneal nerve dysfunction. Among these, impaired corneal innervation plays a particularly critical role, as it disrupts neurotrophic support and tear reflexes, perpetuating disease progression, and delaying healing. However, conventional treatments often provide only temporary symptom relief without addressing underlying tissue damage or promoting nerve regeneration. This shortcoming highlights the need for therapies that not only suppress inflammation but also restore corneal innervation. In this study, we evaluated the therapeutic potential of mesenchymal stem cell (MSC) spheroid-derived secretome—a cell-free solution rich in regenerative and anti-inflammatory factors—in a preclinical mouse model of dry eye disease. Compared with untreated controls, eyes treated with the MSC spheroid secretome presented faster corneal epithelial regeneration, improved corneal nerve reinnervation, and reduced inflammatory cell infiltration. These findings demonstrate that the MSC spheroid-derived secretome can simultaneously target multiple pathological features of dry eye to promote recovery of ocular surface integrity, underscoring its potential as a clinically relevant, cell-free regenerative therapy for dry eye and other ocular surface disorders. |
| format | Article |
| id | doaj-art-37e2ff898a7f4414bfa4c5375b0cbe88 |
| institution | Kabale University |
| issn | 2041-7314 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Journal of Tissue Engineering |
| spelling | doaj-art-37e2ff898a7f4414bfa4c5375b0cbe882025-08-20T03:44:18ZengSAGE PublishingJournal of Tissue Engineering2041-73142025-08-011610.1177/20417314251363300Spheroid assembly of mesenchymal stem cells enhances secretome-mediated corneal reinnervation and epithelial repair in a mouse model of experimental dry eyeShao-Wen Liu0Meng-Yu Tsai1Yang-Chun Shen2Yi-Jen Hsueh3Han Chiu4Li-Wen Hsu5Hung-Chi Chen6Chieh-Cheng Huang7Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, TaiwanInstitute of Biomedical Engineering, National Tsing Hua University, Hsinchu, TaiwanInstitute of Biomedical Engineering, National Tsing Hua University, Hsinchu, TaiwanInternational PhD Program in Innovative Technology of Biomedical Engineering and Medical Devices, Ming Chi University of Technology, New Taipei City, TaiwanInstitute of Biomedical Engineering, National Tsing Hua University, Hsinchu, TaiwanBioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, TaiwanDepartment of Medicine, Chang Gung University, Taoyuan, TaiwanInstitute of Biomedical Engineering, National Tsing Hua University, Hsinchu, TaiwanDry eye disease is a complex ocular surface disorder with multifactorial pathophysiology, including corneal epithelial damage, chronic inflammation, and corneal nerve dysfunction. Among these, impaired corneal innervation plays a particularly critical role, as it disrupts neurotrophic support and tear reflexes, perpetuating disease progression, and delaying healing. However, conventional treatments often provide only temporary symptom relief without addressing underlying tissue damage or promoting nerve regeneration. This shortcoming highlights the need for therapies that not only suppress inflammation but also restore corneal innervation. In this study, we evaluated the therapeutic potential of mesenchymal stem cell (MSC) spheroid-derived secretome—a cell-free solution rich in regenerative and anti-inflammatory factors—in a preclinical mouse model of dry eye disease. Compared with untreated controls, eyes treated with the MSC spheroid secretome presented faster corneal epithelial regeneration, improved corneal nerve reinnervation, and reduced inflammatory cell infiltration. These findings demonstrate that the MSC spheroid-derived secretome can simultaneously target multiple pathological features of dry eye to promote recovery of ocular surface integrity, underscoring its potential as a clinically relevant, cell-free regenerative therapy for dry eye and other ocular surface disorders.https://doi.org/10.1177/20417314251363300 |
| spellingShingle | Shao-Wen Liu Meng-Yu Tsai Yang-Chun Shen Yi-Jen Hsueh Han Chiu Li-Wen Hsu Hung-Chi Chen Chieh-Cheng Huang Spheroid assembly of mesenchymal stem cells enhances secretome-mediated corneal reinnervation and epithelial repair in a mouse model of experimental dry eye Journal of Tissue Engineering |
| title | Spheroid assembly of mesenchymal stem cells enhances secretome-mediated corneal reinnervation and epithelial repair in a mouse model of experimental dry eye |
| title_full | Spheroid assembly of mesenchymal stem cells enhances secretome-mediated corneal reinnervation and epithelial repair in a mouse model of experimental dry eye |
| title_fullStr | Spheroid assembly of mesenchymal stem cells enhances secretome-mediated corneal reinnervation and epithelial repair in a mouse model of experimental dry eye |
| title_full_unstemmed | Spheroid assembly of mesenchymal stem cells enhances secretome-mediated corneal reinnervation and epithelial repair in a mouse model of experimental dry eye |
| title_short | Spheroid assembly of mesenchymal stem cells enhances secretome-mediated corneal reinnervation and epithelial repair in a mouse model of experimental dry eye |
| title_sort | spheroid assembly of mesenchymal stem cells enhances secretome mediated corneal reinnervation and epithelial repair in a mouse model of experimental dry eye |
| url | https://doi.org/10.1177/20417314251363300 |
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