The protective role of FTY720 in promoting survival of allograft fat in mice

Kaohsiung J Med Sci. 2022 Sep;38(9):889-896. doi: 10.1002/kjm2.12570. Epub 2022 Jul 14.

Abstract

Fat transplantation is widely used for soft-tissue filling and wound repair. Owing to the biological changes in adipocytes in some metabolic diseases, allograft fat can provide a better source of donor fat than autologous fat. Fingolimod (FTY720) possesses a powerful immunomodulatory function. This study aimed to investigate the protective effect of FTY720 in allogeneic fat transplantation. C57BL/6J mice that received allografts were randomly divided into two groups and treated with saline and FTY720, respectively. Fat graft samples were obtained at 1, 6, and 20 weeks posttransplantation. Graft volumes, graft structure, and immune cells were estimated using histological examination, immunohistochemistry, staining immunofluorescence (IF), and quantitative real-time polymerase chain reaction (qRT-PCR). Inflammatory cytokine mRNA expression in grafts was detected by qRT-PCR. FTY720 treatment significantly enhanced allograft retention, structural integrity, and neovascularization, thereby demonstrating the potential of FTY720 in improving graft survival. Further IF staining showed that FTY720 increased regulatory T cell infiltration and reduced macrophage infiltration to some extent. FTY720 treatment also enhanced the expression of the anti-inflammatory cytokines interleukin (IL)-4 and IL-10 and weakened the expression of the pro-inflammatory cytokines TNF-α and IL-6. Furthermore, FTY720 treatment upregulated the expression of CD31 positive cells. This study demonstrated the potential efficacy of FTY720 in improving the graft survival rate of syngeneic fat allograft models, possibly by suppressing immune rejection and promoting angiogenesis. Therefore, this study offers key insights into the potential application of a drug-assisted strategy to prolong allograft fat survival.

Keywords: FTY720; allograft; fat survival; graft; inflammatory cells.

Publication types

  • Randomized Controlled Trial, Veterinary

MeSH terms

  • Allografts
  • Animals
  • Cytokines
  • Fingolimod Hydrochloride* / pharmacology
  • Fingolimod Hydrochloride* / therapeutic use
  • Graft Rejection / drug therapy
  • Graft Rejection / prevention & control
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Propylene Glycols* / pharmacology
  • Propylene Glycols* / therapeutic use
  • Sphingosine / pharmacology

Substances

  • Cytokines
  • Immunosuppressive Agents
  • Propylene Glycols
  • Fingolimod Hydrochloride
  • Sphingosine