# Secretome from Uterine Cervical Mesenchymal Stem Cells as a Protector of Neuronal Cells Against Oxidative Stress and Inflammation

**Authors:** Javier Mateo, Miguel Ángel Suárez-Suárez, Maria Fraile, Ángel Ramón Piñera-Parrilla, Francisco J. Vizoso, Noemi Eiro

PMC · DOI: 10.3390/biom15101402 · Biomolecules · 2025-10-02

## TL;DR

This study shows that the secretome of uterine cervical stem cells protects nerve cells from damage caused by oxidative stress and inflammation.

## Contribution

The study demonstrates the neuroprotective potential of hUCESC secretome in oxidative stress and inflammation models.

## Key findings

- hUCESC-CM increased anti-oxidative stress genes HO-1 and Nrf2 in PC-12 cells.
- hUCESC-CM reduced pro-inflammatory genes IL1β, IL6, and TNFα in both PC-12 and HMC3 cells.
- hUCESC-CM enhanced neuroprotective factors BDNF and GDNF in HMC3 cells.

## Abstract

Background: The limited self-repair capacity of nerve tissue requires a new therapeutic approach. Mesenchymal stem cells from the uterine cervix, hUCESC, have shown anti-inflammatory, regenerative, and anti-oxidative stress effects through their secretome, which makes them candidates to evaluate their potential in the context of neuronal damage. In this study, we aimed to determine whether secretome or conditioned medium of hUCESC (hUCESC-CM) has beneficial action in the treatment of PC-12 and HMC3 cells in vitro under conditions of oxidative stress and inflammation. Methods: Differentiated PC-12 cells and HMC3 cells were subjected to oxidative stress and inflammatory conditions in the presence of hUCESC-CM. The expression of factors related to both processes was evaluated by q-RT-PCR. Results: PC-12 cells treated with hUCESC-CM showed a significant increase in the expression of anti-oxidative stress factors (HO-1 and Nrf2) and a significant decrease in the expression of pro-inflammatory factors (IL1β, IL6 and TNFα). In addition, the treatment of HMC3 cells with hUCESC-CM significantly decreased the expression of IL6 and TNFα and enhanced the expression of neuroprotective factors such as BDNF and GDNF. Conclusions: Considering that both oxidative stress and inflammation are interrelated and implicated in several nerve injuries and neurodegenerative disorders, the effects of hUCESC-CM on neuronal cells are very promising.

## Linked entities

- **Genes:** HMOX1 (heme oxygenase 1) [NCBI Gene 3162], GABPA (GA binding protein transcription factor subunit alpha) [NCBI Gene 2551], IL1B (interleukin 1 beta) [NCBI Gene 3553], IL6 (interleukin 6) [NCBI Gene 3569], TNF (tumor necrosis factor) [NCBI Gene 7124], BDNF (brain derived neurotrophic factor) [NCBI Gene 627], GDNF (glial cell derived neurotrophic factor) [NCBI Gene 2668]

## Full-text entities

- **Genes:** NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, GDNF (glial cell derived neurotrophic factor) [NCBI Gene 2668] {aka ATF, ATF1, ATF2, HFB1-GDNF, HSCR3}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}
- **Diseases:** neuronal damage (MESH:D009410), Inflammation (MESH:D007249), neurodegenerative disorders (MESH:D019636), nerve injuries (MESH:D000080902)
- **Chemicals:** hUCESC (-)
- **Cell lines:** HMC3 — Homo sapiens (Human), Transformed cell line (CVCL_II76), PC-12 — Rattus norvegicus (Rat), Rat adrenal gland pheochromocytoma, Cancer cell line (CVCL_0481)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12562245/full.md

## References

64 references — full list in the complete paper: https://tomesphere.com/paper/PMC12562245/full.md

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Source: https://tomesphere.com/paper/PMC12562245