Wound-Healing Effects of Mesenchymal Stromal Cell Secretome in the Cornea and the Role of Exosomes
Mesenchymal stromal/stem cells (MSCs) and their secreted factors have been shown to have immunomodulatory and regenerative effects. In this study, we investigated human bone-marrow-derived MSC secretome (MSC-S) for the treatment of corneal epithelial wounds. Specifically, we evaluated the role of MS...
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| Format: | Article |
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MDPI AG
2023-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/5/1486 |
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| author | Seungwon An Khandaker Anwar Mohammadjavad Ashraf Hyungjo Lee Rebecca Jung Raghuram Koganti Mahmood Ghassemi Ali R. Djalilian |
| author_facet | Seungwon An Khandaker Anwar Mohammadjavad Ashraf Hyungjo Lee Rebecca Jung Raghuram Koganti Mahmood Ghassemi Ali R. Djalilian |
| author_sort | Seungwon An |
| collection | DOAJ |
| description | Mesenchymal stromal/stem cells (MSCs) and their secreted factors have been shown to have immunomodulatory and regenerative effects. In this study, we investigated human bone-marrow-derived MSC secretome (MSC-S) for the treatment of corneal epithelial wounds. Specifically, we evaluated the role of MSC extracellular vesicles (EV)/exosomes in mediating the wound-healing effects of the MSC-S. In vitro studies using human corneal epithelial cells showed that MSC-CM increased cell proliferation in HCEC and HCLE cells, while EV-depleted MSC-CM showed lower cell proliferation in both cell lines compared to the MSC-CM group. In vitro and in vivo experiments revealed that 1X MSC-S consistently promoted wound healing more effectively than 0.5X MSC-S, and MSC-CM promoted wound healing in a dose-dependent manner, while exosome deprivation delayed wound healing. We further evaluated the incubation period of MSC-CM on corneal wound healing and showed that MSC-S collected for 72 h is more effective than MSC-S collected for 48 h. Finally, we evaluated the stability of MSC-S under different storage conditions and found that after one cycle of freeze–thawing, MSC-S is stable at 4 °C for up to 4 weeks. Collectively, we identified the following: (i) MSC-EV/Exo as the active ingredient in MSC-S that mediates the wound-healing effects in the corneal epithelium, providing a measure to optimize its dosing for a potential clinical product; (ii) Treatment with EV/Exo-containing MSC-S resulted in an improved corneal barrier and decreased corneal haze/edema relative to EV/Exo-depleted MSC-S; (iii) The stability of MSC-CM for up to 4 weeks showed that the regular storage condition did not significantly impact its stability and therapeutic functions. |
| first_indexed | 2024-03-11T03:24:27Z |
| format | Article |
| id | doaj.art-785c44d8a8634d13a35bedab39f693f8 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T03:24:27Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-785c44d8a8634d13a35bedab39f693f82023-11-18T02:52:17ZengMDPI AGPharmaceutics1999-49232023-05-01155148610.3390/pharmaceutics15051486Wound-Healing Effects of Mesenchymal Stromal Cell Secretome in the Cornea and the Role of ExosomesSeungwon An0Khandaker Anwar1Mohammadjavad Ashraf2Hyungjo Lee3Rebecca Jung4Raghuram 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, USAMesenchymal stromal/stem cells (MSCs) and their secreted factors have been shown to have immunomodulatory and regenerative effects. In this study, we investigated human bone-marrow-derived MSC secretome (MSC-S) for the treatment of corneal epithelial wounds. Specifically, we evaluated the role of MSC extracellular vesicles (EV)/exosomes in mediating the wound-healing effects of the MSC-S. In vitro studies using human corneal epithelial cells showed that MSC-CM increased cell proliferation in HCEC and HCLE cells, while EV-depleted MSC-CM showed lower cell proliferation in both cell lines compared to the MSC-CM group. In vitro and in vivo experiments revealed that 1X MSC-S consistently promoted wound healing more effectively than 0.5X MSC-S, and MSC-CM promoted wound healing in a dose-dependent manner, while exosome deprivation delayed wound healing. We further evaluated the incubation period of MSC-CM on corneal wound healing and showed that MSC-S collected for 72 h is more effective than MSC-S collected for 48 h. Finally, we evaluated the stability of MSC-S under different storage conditions and found that after one cycle of freeze–thawing, MSC-S is stable at 4 °C for up to 4 weeks. Collectively, we identified the following: (i) MSC-EV/Exo as the active ingredient in MSC-S that mediates the wound-healing effects in the corneal epithelium, providing a measure to optimize its dosing for a potential clinical product; (ii) Treatment with EV/Exo-containing MSC-S resulted in an improved corneal barrier and decreased corneal haze/edema relative to EV/Exo-depleted MSC-S; (iii) The stability of MSC-CM for up to 4 weeks showed that the regular storage condition did not significantly impact its stability and therapeutic functions.https://www.mdpi.com/1999-4923/15/5/1486mesenchymal stromal cellsmesenchymal stem cell-conditioned mediaexosomesreconstituted–conditioned mediawound healing |
| spellingShingle | Seungwon An Khandaker Anwar Mohammadjavad Ashraf Hyungjo Lee Rebecca Jung Raghuram Koganti Mahmood Ghassemi Ali R. Djalilian Wound-Healing Effects of Mesenchymal Stromal Cell Secretome in the Cornea and the Role of Exosomes Pharmaceutics mesenchymal stromal cells mesenchymal stem cell-conditioned media exosomes reconstituted–conditioned media wound healing |
| title | Wound-Healing Effects of Mesenchymal Stromal Cell Secretome in the Cornea and the Role of Exosomes |
| title_full | Wound-Healing Effects of Mesenchymal Stromal Cell Secretome in the Cornea and the Role of Exosomes |
| title_fullStr | Wound-Healing Effects of Mesenchymal Stromal Cell Secretome in the Cornea and the Role of Exosomes |
| title_full_unstemmed | Wound-Healing Effects of Mesenchymal Stromal Cell Secretome in the Cornea and the Role of Exosomes |
| title_short | Wound-Healing Effects of Mesenchymal Stromal Cell Secretome in the Cornea and the Role of Exosomes |
| title_sort | wound healing effects of mesenchymal stromal cell secretome in the cornea and the role of exosomes |
| topic | mesenchymal stromal cells mesenchymal stem cell-conditioned media exosomes reconstituted–conditioned media wound healing |
| url | https://www.mdpi.com/1999-4923/15/5/1486 |
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