脂肪间充质干细胞与甲泼尼龙联合用药对小型猪异体皮肤移植的影响

doi:10.11843/j.issn.0366-6964.2023.08.037

Abstract

Abstract: The aim of this experiment was to investigate the effect of the combination of adipose derived mesenchymal stem cells (ADSCs) and methylprednisolone (MP) on immune rejection and wound healing in allogeneic skin grafts from miniature pigs. An allogeneic skin graft model was established for 12 minipigs, and the minipigs were randomly and equally divided into four groups according to different postoperative interventions on allogeneic skin graft skin pieces:allogeneic skin graft group (ASG), methylprednisolone group (MP), adipose mesenchymal stem cells (ADSCs), and combined adipose mesenchymal stem cells and methylprednisolone (ADSCs+MP) group.Blood and tissue samples were collected preoperatively and at 7 and 14 d postoperatively, and clinical changes of the grafted epidermis were photographed and recorded immediately, at 7, 14 and 21 d postoperatively. The effects of the four different interventions on the immune rejection and wound healing of allogeneic skin grafts in minipigs were evaluated by the phenological examination, pathological histological examination, blood and serum biochemistry, and the indexes of oxidative stress, inflammation and regeneration of the grafted skin tissues. From the skin slice phenotypic and pathological analysis, it was observed that the survival time of the grafted skin slice was around 7 d in the ASG group, 7-14 d in the MP group, and 14-21 d in the ADSCs and ADSCs+MP groups. and the expression of GSH and SOD was significantly higher in the ADSCs+MP group at 7 and 14 d. In terms of immune rejection, the ADSCs+MP group had significantly higher CD4⁺ T cells, protein and gene expression of NF-κB, and expression of IL-2, IFN-γ, TNF-α, IL-1β, and IL-6 pro-inflammatory factors were significantly lower in the ADSCs+MP group relative to the ASG group.In terms of wound healing, the ADSCs+MP group significantly increased the protein expression of VEGF and TGF-β, and the expression of SDF-1 and CXCR4 relative to the ASG group. the ADSCs+MP group could significantly inhibit the protein and gene expression of PI3K, AKT, and 11β-HSD1. In conclusion, the ADSCs+MP group could prolong the survival time of grafted skin pieces relative to the ASG and MP groups. And ADSCs+MP could effectively inhibit oxidative stress by promoting the expression of GSH and SOD. In terms of rejection, ADSCs+MP can inhibit the expression of inflammatory factors such as IL-2, IFN-γ, IL-6 and TNF-α by suppressing the expression of NF-κB, thus suppressing the immune rejection reaction after transplantation. Moreover, ADSCs+MP could promote wound healing by promoting the expression of healing factors such as VEGF and TGF-β. Further study revealed that ADSCs may affect the expression of 11β-HSD1 by inhibiting PI3K/AKT, which in turn suppresses skin cortisol content and promotes the expression of growth factors such as TGF-β and VEGF to promote wound granulation tissue regeneration and vascular migration.

Key words: mini-pigs, adipose mesenchymal stem cells, allogeneic skin grafts, immune rejection, wound healing, methylprednisolone

CLC Number:

S857.132

JIAO Guangming, LÜ Yingguang, SANG Jinfang, KOU Zhipeng, LIU Tao, WANG Yue, LU Xiangyu, PIAO Chenxi, MA Yajun, ZHANG Jiantao, WANG Hongbin. Effect of Adipose Mesenchymal Stem Cells in Combination with Methylprednisolone on Allogeneic Skin Grafts in Minipigs[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(8): 3533-3545.

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Effect of Adipose Mesenchymal Stem Cells in Combination with Methylprednisolone on Allogeneic Skin Grafts in Minipigs

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