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KMID : 1377020230200060905
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Tissue Engineering and Regenerative Medicine
2023 Volume.20 No. 6 p.905 ~ p.919
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Multiple Injections of Adipose-Derived Stem Cells Improve Graft Survival in Human-to-Rat Skin Xenotransplantation through Immune Modulation
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Jeon Sung-Mi
Kim Il-Jin
Na Yi-Rang
Hong Ki-Yong
Chang Hak
Kim Seung-Hwan
Jeong Yu-Jin
Chung Jee-Hyeok
Kim Sang-Wha
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Abstract
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Background : Adipose-derived stem cells (ADSCs) exert immunomodulatory effects in the treatment of transplant rejection. This study aimed to evaluate the effects of ADSCs on the skin graft survival in a human-to-rat xenograft transplantation model and to compare single and multiple injections of ADSCs.
Methods : Full-thickness human skin xenografts were transplanted into the backs of Sprague?Dawley rats. The rats were injected subcutaneously on postoperative days 0, 3, and 5. The injections were as follows: triple injections of phosphate-buffered saline (PBS group), a single injection of ADSCs and double injections of PBS (ADSC?×?1 group), and triple injections of ADSCs (ADSC?×?3 group). The immunomodulatory effects of ADSCs on human skin xenografts were assessed.
Results : Triple injections of ADSCs considerably delayed cell-mediated xenograft rejection compared with the PBS and ADSC?×?1 groups. The vascularization and collagen type 1?3 ratios in the ADSC?×?3 group were significantly higher than those in the other groups. In addition, intragraft infiltration of CD3-, CD4-, CD8-, and CD68-positive cells was reduced in the ADSC?×?3 group. Furthermore, in the ADSC?×?3 group, the expression levels of proinflammatory cytokine interferon-gamma (IFN-γ) were decreased and immunosuppressive prostaglandin E synthase (PGES) was increased in the xenograft and lymph node samples.
Conclusion : This study presented that triple injections of ADSCs appeared to be superior to a single injection in suppressing cell-mediated xenograft rejection. The immunomodulatory effects of ADSCs are associated with the downregulation of IFN-γ and upregulation of PGES in skin xenografts and lymph nodes.
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KEYWORD
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Adipose-derived stem cells, Skin xenograft, IFN-c, PGES
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