Adipose-derived stem cells regulate CD4+ T-cell-mediated macrophage polarization and fibrosis in fat grafting in a mouse model

Abstract

Autologous fat grafting is becoming increasingly common worldly. However, the long-term retention of fat grafting is still unpredictable due to the inevitable fibrosis arising during tissue repair. Fibrosis may be regulated by T-cell immune responses that are influenced by adipose-derived stem cells (ASCs). Therefore, we hypothesized that overly abundant ASCs might promote fibrosis by promoting T-cell immune responses to adipose tissue. We performed 0.3 ml fat grafts with 104/ml, 106/ml and 108/ml ASCs and control group in C57 BL/6 mice in vivo. We observed retention, fibrosis, T-cell immunity, and macrophage infiltration over 12 weeks. Besides, CD4+ T-helper 1 (Th1) cells and T-helper 2 (Th2) cells were co-cultured with ASCs or ASCs conditioned media (ASCs-CM) in vitro. We detected the ratio of Th2%/Th1%. Results showed that the retention rate was higher in 104 group, while even lower in 108 group with significantly increased inflammation and fibrosis than control group at week 12 in vivo. There was no significance between control group and 106 group. Also, 108 group increased the infiltration of M2 macrophages, CD4+ T-cells and Th2/Th1 ratio. In vitro, the ratio of Th2%/Th1% induced by ASCs-transwell group was higher than ASCs-CM group and showed concentration-dependent. Accordingly, high concentrations of ASCs in adipose tissue can promote Th1–Th2 shifting, and excessive Th2 cells might promote the persistence of M2 macrophages and increase the level of fibrosis which lead to a decrease in the long-term retention of fat grafts. Also, we found ASCs promoted Th1–Th2 shifting in vitro.

Keywords

• Adipose-derived stem cell
• Fibrosis
• Fat grafting
• CD4+ T-cell
• Macrophage