# The efficacy of bone marrow-derived mesenchymal stem cells in restoring limbal stem cell deficiency in rat model

**Authors:** Mohamed A. El-Desouky, Nadia Samy Mahmoud, Fayek M. Ghaleb, Fatma B. Rashidi, Iman M. A. Zaki, Marwa A. Fouly, Ahmed M. Ata, Hanaa Hamdy Ahmed

PMC · DOI: 10.1038/s41598-025-26637-2 · Scientific Reports · 2025-11-20

## TL;DR

This study shows that bone marrow-derived stem cells can help repair corneal damage in rats by reducing inflammation and improving healing.

## Contribution

The study demonstrates the novel use of BM-MSCs in treating limbal stem cell deficiency through anti-inflammatory and tissue repair mechanisms.

## Key findings

- BM-MSCs treatment improved corneal wound healing and reduced opacity and neovascularization.
- BM-MSCs significantly decreased inflammatory markers like TNF-α and IL-8.
- Stem cell treatment restored corneal epithelial integrity and reduced apoptosis.

## Abstract

This approach aimed to assess the therapeutic significance of BM-MSCs in alleviating LSCD elicited in rats via corneal alkali burns and to explore the associated repairing mechanisms. Rats were assigned to (1) control group, (2) alkali burn group, and (3) stem cells group. Corneal surface investigations were performed using a slit lamp and fluorescence tests. The therapeutic impact of BM-MSCs was appraised by estimating the protein levels of TNF-α, SOD, VEGF, MMP-2, and IL-8 using ELISA. Moreover, mRNA transcription levels of corneal TNF-α, NF-kB, COX-2, and caspase-3 were quantified. Histological investigation and immunostaining of corneal cytokeratin 3 and p63 proteins were also conducted. The results indicated that BM-MSCs treatment enhanced the corneal wound healing, decreased corneal opacity, and neovascularization. Moreover, such treatment resulted in a significant decline in corneal TNF-α, IL-8, VEGF, and MMP-2 protein levels. Additionally, stem cells group elicited a significant down-expression of TNF-α, NF-κB, COX-2, and caspase-3 genes. Besides, BM-MSCs treatment restored the corneal epithelial integrity and ameliorated the pathological characteristics, as confirmed by histological and immunohistochemical analysis. Conclusively, the present investigation underscores the healing ability of BM-MSCs in LSCD in the rat model by repairing the damaged corneal epithelium through withstanding inflammation, angiogenesis, and apoptosis. Consequently, MSCs transplantation represents a promising therapeutic modality for LSCD.

The online version contains supplementary material available at 10.1038/s41598-025-26637-2.

## Linked entities

- **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124], SOD1 (superoxide dismutase 1) [NCBI Gene 6647], VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422], MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313], CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576], TNF (tumor necrosis factor) [NCBI Gene 7124], NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790], COX2 (cytochrome c oxidase subunit II) [NCBI Gene 4513], Casp3 (caspase 3) [NCBI Gene 12367]
- **Proteins:** TNF (tumor necrosis factor), SOD1 (superoxide dismutase 1), VEGFA (vascular endothelial growth factor A), MMP2 (matrix metallopeptidase 2), CXCL8 (C-X-C motif chemokine ligand 8), RPE65 (retinoid isomerohydrolase RPE65)
- **Diseases:** limbal stem cell deficiency (MONDO:0025667)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Mmp2 (matrix metallopeptidase 2) [NCBI Gene 81686], Vegfa (vascular endothelial growth factor A) [NCBI Gene 83785] {aka VEGF-A, VEGF111, VEGF164, VPF, Vegf}, Casp3 (caspase 3) [NCBI Gene 25402] {aka CPP32-beta, Lice, Yama}, Rela (RELA proto-oncogene, NF-kB subunit) [NCBI Gene 309165] {aka NFkB, nos2}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Ptgs2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 29527] {aka COX-2, Cox2, PGHS-2, PHS II, Pghs2}
- **Diseases:** corneal alkali burns (MESH:D006934), inflammation (MESH:D007249), stem cell deficiency (MESH:D000092423), corneal opacity (MESH:D003318)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12638304/full.md

## References

12 references — full list in the complete paper: https://tomesphere.com/paper/PMC12638304/full.md

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Source: https://tomesphere.com/paper/PMC12638304