Potential Therapeutic Effects of Epithelial and Mesenchymal Stem Cell Secretome in Benzalkonium Chloride-Induced Limbal Stem Cell Dysfunction

TL;DR

Stem cell secretions can protect eye stem cells damaged by a common preservative in eye drops, with better results when used alongside the preservative.

Contribution

Demonstrates that stem cell-derived conditioned media can neutralize benzalkonium chloride toxicity in limbal stem cells, with concurrent administration being more effective.

Findings

Conditioned media from hADSCs, hAECs, and hACs reduce BAC-induced damage to limbal stem cells.

Concurrent administration of CM with BAC exposure is more effective than post-damage treatment.

hADSC-derived CM shows the highest efficacy in promoting LSC regeneration.

Abstract

What are the main conclusions?

Conditioned media (CM) derived from adipose tissue-derived stem cells (hADSCs), amniotic epithelial cells (hAECs), and amniotic cells expressing epithelial and mesenchymal markers (hACs) promote the viability of limbal stem cells (LSCs) damaged by benzalkonium chloride (BAC), a commonly used eye drop.

The effects of these CM administered concurrently with BAC (model 1) or after prior tissue damage with BAC (model 2) differ in terms of modulating inflammation, apoptosis, cell cycle, proliferation, and migration of LSCs.

What are the implications of the main conclusions?

All CM tested neutralize the toxic effects of BAC, but hADSC-CM demonstrates the highest efficacy.

Administration of CM concurrently with BAC exposure has greater therapeutic potential than the treatment used after toxic injury.

These findings highlight the promising role of acellular stem cell-based therapies in ophthalmic diseases.

Dry Eye Disease (DED) is a multifactorial condition of the ocular surface, with one potential cause being damage from eye drops containing preservatives such as benzalkonium chloride (BAC). Current treatments for DED are unsatisfactory; therefore, it is worth exploring new therapies based on the secretome derived from stem cells. Human stem cells are important sources of growth factors and cytokines that promote tissue regeneration. The secretome of these cells can be obtained in vitro in conditioned medium (CM). The aim of the study was to evaluate the effect of CM derived from adipose-derived stem cells (hADSCs) and amniotic membrane-derived cells expressing mesenchymal and/or epithelial markers on limbal stem cells (LSCs) damaged by BAC, focusing on their regenerative potential. The study used two experimental models: the first focused on neutralizing the toxic effects of BAC when each CM was administered concurrently, and the second on the therapeutic effects of CM after prior cell damage by BAC. The effects of CM on LSCs were assessed, including apoptosis, cell cycle progression, proliferation, migration, and inflammation. CM from ADSCs and amniotic cells were shown to significantly reduce BAC-induced damage to LSCs. All tested CM promoted LSC regeneration, although their efficacy varied among treatments. The application of CM during BAC exposure yielded stronger and more consistent benefits than post-injury treatment.

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