Preventing the rejection of skin allografts by immunomodulatory and regenerative effects of exosomes derived from bone marrow mesenchymal stem cells in mice

Document Type : Original Article

Authors

1 Biomedical Research Institute, University of Tehran, Tehran, Iran

2 Gene Therapy Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Microbiology and Immunology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

4 Department of Surgery and Radiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

5 Department of Tissue Engineering and Applied Cell Sciences, School of Medicine, Qom University of Medical Sciences, Qom, Iran

6 Department of Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

7 Department of Internal Medicine, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

Abstract

Objective(s): Reducing the immune response to inflammation is vital for successful transplantation, yet chronic graft rejection remains a major issue despite immunosuppressive drugs. This study explored the effect of bone marrow mesenchymal stem cell-derived exosomes on the survival of skin allografts in mice.
Materials and Methods: C57BL/6 and BALB/c mice underwent skin allograft surgery, followed by intraperitoneal injection of exosomes, which were compared with groups receiving dexamethasone and no treatment group.
Results: On day 3, mild signs of graft rejection appeared in both control groups, while none were seen in the exosome-treated group. By day 14, the grafts were completely rejected in the control groups but showed mild rejection in the treatment group. Histopathology revealed severe rejection signs in the control groups, including epithelial necrosis and inflammation, while the treatment group showed signs of angiogenesis and graft acceptance. Additionally, inflammatory cytokine levels (TNF-α, IL-1β, and IL-6) were lower in the treatment group than in the positive control group, particularly on days 3 and 14.
Conclusion: The findings suggest that exosomes can prevent graft rejection and may offer a promising therapeutic approach for solid organ transplantation, though further research is needed to standardize exosome methods and evaluate cost-effectiveness.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences
Volume 28, Issue 4
April 2025
Pages 469-476

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