Extracellular Vesicles Isolated from Equine Adipose-Derived Stromal Stem Cells (ASCs) Mitigate Tunicamycin-Induced ER Stress in Equine Corneal Stromal Stem Cells (CSSCs).

Meissner, JM
·
Chmieliu0144ska, A
·
Ofri, R
·
Cisu0142o-Sankowska, A
·
Marycz, K

Abstract: Corneal ulcers, characterized by severe inflammation of the cornea, can lead to serious, debilitating complications and may be vision-threatening for horses. In this study, we aimed to investigate the role of endoplasmic reticulum (ER) stress in corneal stem progenitor cell (CSSC) dysfunction and explore the potential of equine adipose-derived stromal stem cell (ASC)-derived extracellular vesicles (EVs) to improve corneal wound healing. We showed that CSSCs expressed high levels of CD44, CD45, and CD90 surface markers, indicating their stemness. Supplementation of the ER-stress-inducer tunicamycin to CSSCs resulted in reduced proliferative and migratory potential, accumulation of endoplasmic reticulum (ER)-stressed cells in the G0/G1 phase of the cell cycle, increased expression of proinflammatory genes, induced oxidative stress and sustained ER stress, and unfolded protein response (UPR). Importantly, treatment with EVs increased the proliferative activity and number of cells in the G2/Mitosis phase, enhanced migratory ability, suppressed the overexpression of proinflammatory cytokines, and upregulated the anti-inflammatory , compared to control and/or ER-stressed cells. Additionally, EVs lowered the expression of ER-stress master regulators and effectors (, , , and ), increased the number of mitochondria, and reduced the expression of and , thereby promoting metabolic homeostasis and protecting against apoptosis in equine CSSCs. Our findings demonstrate that MSCs-derived EVs represent an innovative and promising therapeutic strategy for the transfer of bioactive mediators which regulate various cellular and molecular signaling pathways.

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Publication Date: 2024-04-09 PubMed ID: 38666934PubMed Central: PMC11048834DOI: 10.3390/cimb46040204Google Scholar: Lookup

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This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article investigates the use of stem-cell derived extracellular vesicles in treating corneal ulcers in horses. The study finds these vesicles can improve cell function, reduce inflammation, and potentially enhance wound healing.

Understanding Corneal Ulcers and Stem Cells

The study starts by explaining the severity of corneal ulcers, which can lead to debilitating complications and potentially vision loss in horses. This research primarily focused on how endoplasmic reticulum (ER) stress in cells can impact the development and treatment of these corneal ulcers.
To improve our understanding of ER stress, the study explored the potential of extracellular vesicles (EVs) derived from equine adipose-derived stromal stem cells (ASC) to advance the healing of corneal wounds.
Using cell markers, the researchers determined that corneal stromal progenitor cells (CSSCs) exhibit high stemness, are essentially, they are capable of self-renewal and differentiation into other cell types.

Investigation of ER Stress and Its Impact

The researchers introduced ER-stress-inducer tunicamycin to CSSCs, which resulted in several adverse outcomes, including a reduction in cell proliferation and migration.
It led to an accumulation of ER-stressed cells in the G0/G1 phase of the cell cycle, an increase in the expression of proinflammatory genes, and a sustained ER stress response.
This sequence of events induced oxidative stress, impacting the overall health of the cells in question.

The Role of Extracellular Vesicles (EVs)

The treatment with EVs derived from adipose-derived stromal stem cells (ASCs) yielded remarkable results, including the enhancement of the proliferative activity of CSSCs, and an increase in the number of cells in the G2/Mitosis phase of the cell cycle.
The EVs enhanced the migratory capability of cells, suppressed the overexpression of proinflammatory cytokines, and upregulated anti-inflammatory agents.
The study also found EVs reduced the expression of ER-stress master regulators and effectors, increased mitochondria numbers, and decreased apoptosis (programmed cell death), thus promoting metabolic balance.

Conclusion

The research discussed suggests that extracellular vesicles derived from mesenchymal stem cells (MSCs) could provide a novel therapeutic strategy for the treatment of corneal ulcers.
These vesicles can transfer bioactive mediators, which have the potential to regulate various cellular and molecular signaling pathways, thereby alleviating ER stress and promoting overall cellular health.
In particular, they hold promise for improving aspects of corneal wound healing in horses and potentially other animals.

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APA

Meissner JM, Chmieliu0144ska A, Ofri R, Cisu0142o-Sankowska A, Marycz K. (2024). Extracellular Vesicles Isolated from Equine Adipose-Derived Stromal Stem Cells (ASCs) Mitigate Tunicamycin-Induced ER Stress in Equine Corneal Stromal Stem Cells (CSSCs). Curr Issues Mol Biol, 46(4), 3251-3277. https://doi.org/10.3390/cimb46040204

Publication

Current issues in molecular biology

ISSN: 1467-3045

NlmUniqueID: 100931761

Country: Switzerland

Language: English

Volume: 46

Issue: 4

Pages: 3251-3277

Researcher Affiliations

Meissner, Justyna M

Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocu0142aw University of Environmental and Life Sciences, Norwida 27B, 50-375 Wroclaw, Poland.

Chmieliu0144ska, Aleksandra

International Institute of Translational Medicine, Jesionowa 11, Malin, 55-114 Wisznia Mala, Poland.

Ofri, Ron

Koret School of Veterinary Medicine, Hebrew University of Jerusalem, P.O. Box 12, Rehovot 7610001, Israel.

Cisu0142o-Sankowska, Anna

International Institute of Translational Medicine, Jesionowa 11, Malin, 55-114 Wisznia Mala, Poland.

Marycz, Krzysztof

Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocu0142aw University of Environmental and Life Sciences, Norwida 27B, 50-375 Wroclaw, Poland.
International Institute of Translational Medicine, Jesionowa 11, Malin, 55-114 Wisznia Mala, Poland.
Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95516, USA.

Conflict of Interest Statement

The authors declare no conflicts of interest.

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