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  3. Adipose-derived stem cells inhibit dendritic cell migration by secreting tumor necrosis factor-α-stimulated gene 6 to improve the allogeneic skin transplantation survival rate in mice

Adipose-derived stem cells inhibit dendritic cell migration by secreting tumor necrosis factor-α-stimulated gene 6 to improve the allogeneic skin transplantation survival rate in mice

  • Cell Transplant. 2025 Jan-Dec:34:9636897251376125. doi: 10.1177/09636897251376125.
Julong Hu 1 2,  Wenxu Peng 1,  Yeltai Nurzat 1 2,  Qi Zhang 1,  Zaihuan Lin 1,  Jianlei Xie 1,  Meiqian Xu 1,  Hang Ji 2,  Gang Liang 2,  Zhihua Zhang 2,  Wenjing Liao 1,  Xiaowen Zhang 1 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Respiratory Disease, Laboratory of ENT-HNS Disease, Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • 2 Department of Plastic and Reconstructive Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • 3 Department of Allergy and Clinical Immunology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
PMID: 41108126 DOI: 10.1177/09636897251376125
Abstract

Allogeneic skin transplantation faces significant immunological challenges due to immune rejection, primarily mediated by dendritic cells (DCs). Adipose-derived stem cells (ADSCs) possess immunomodulatory effects; however, the underlying molecular mechanisms in regulating DC function remain unclear. This study aimed to investigate the regulatory effects of ADSCs and tumor necrosis factor-α-stimulated gene 6 (TSG-6) secreted by ADSCs on DC in the murine allogeneic skin transplantation. Following transplantation, recipients received ADSCs, TSG-6 knockdown ADSCs (ADSCs-shTSG-6), or control treatments. Immune cell infiltration and cytokine expression were analyzed by flow cytometry and immunohistochemistry. Transwell assays were used to assess the effect of TSG-6 on DCs migration. TSG-6-related gene expression profiles were explored using transcriptomic analysis and validated by RT-qPCR. ADSC treatment significantly reduced the migration of DCs to the recipient than the ADSCs-shTSG-6 treatment, while reducing the levels of macrophages, lymphocytes, and pro-inflammatory cytokines. ADSC-derived TSG-6 inhibited DCs migration, an effect diminished upon TSG-6 knockdown and restored by TSG-6 supplementation. Transcriptomic analysis identified a panel of immune-related genes (ADM, GHRH, SELENBP1, NDRG1) regulated by TSG-6. These findings indicate that ADSCs enhance graft tolerance by inhibiting DCs migration via TSG-6 secretion, highlighting TSG-6 as a promising therapeutic target for preventing transplant rejection.

Keywords

adipose-derived stem cells; allogeneic skin graft; dendritic cells; immune modulation; tumor necrosis factor-α-stimulated gene 6.

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