Effect of Stem Cell-Derived Extracellular Vesicles on Damaged Human Corneal Endothelial Cells

Overview

Journal Stem Cells Int

Publisher Wiley

Specialty Cell Biology

Date 2021 Feb 3

PMID 33531909

Citations 17

Authors

Raffaele Nuzzi

Lola Buono

Simona Scalabrin

Marco De Iuliis

Benedetta Bussolati

Affiliations

Soon will be listed here.

Abstract

Purpose: Human corneal endothelial cells (HCECs) are essential to visual function; however, since they have limited proliferative capacity , they are prone to corneal endothelial dysfunction. At present, the only treatment is a corneal transplantation from donor cadavers. Also, due to a global shortage of donor corneas, it is important to find alternative strategies. Recent studies highlight that stem cell-derived extracellular vesicles (EVs) play a relevant role in stem cell-induced regeneration by reprogramming injured cells and inducing proregenerative pathways. The aim of this work is to evaluate whether EVs derived from mesenchymal stem cells (MSC-EVs) are able to promote regeneration of damaged HCECs.

Methods: We isolated HCECs from discarded corneas in patients undergoing corneal transplantation or enucleation ( = 23 patients). Bone marrow mesenchymal stem cells (MSCs) were obtained from Lonza, cultured, and characterized. MSC-EVs were obtained from supernatants of MSCs. In order to establish a valid damage model to test the regenerative potential of EVs on HCECs, we evaluated the proliferation rate and the apoptosis after exposing the cells to serum-deprived medium at different concentrations for 24 hours. We then evaluated the HCEC migration through a wound healing assay.

Results: In the selected serum deprivation damage conditions, the treatment with different doses of MSC-EVs resulted in a significantly higher proliferation rate of HCECs at all the tested concentrations of EVs (5-20 × 10 MSC-EV/cell). MSC-EVs/cell induced a significant decrease in number of total apoptotic cells after 24 hours of serum deprivation. Finally, the wound healing assay showed a significantly faster repair of the wound after HCEC treatment with MSC-EVs.

Conclusions: Results highlight the already well-known proregenerative potential of MSC-EVs in a totally new biological model, the endothelium of the cornea. MSC-EVs, indeed, induced proliferation and survival of HCECs, promoting the migration of HCECs .

Citing Articles

Biomedical Application of MSCs in Corneal Regeneration and Repair.

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Mesenchymal stem cell-derived extracellular vesicles for cell-free therapy of ocular diseases.

Liu X, Hu L, Liu F Extracell Vesicles Circ Nucl Acids. 2024; 3(2):102-117.

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The Role of Mesenchymal Stem Cells for Corneal Endothelial Regeneration: A Systematic Review.

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Molecular and Cellular Mechanisms of the Therapeutic Effect of Mesenchymal Stem Cells and Extracellular Vesicles in Corneal Regeneration.

Kobal N, Marzidovsek M, Schollmayer P, Malicev E, Hawlina M, Marzidovsek Z Int J Mol Sci. 2024; 25(20).

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