Transforming growth factor-beta1 inhibits tissue engineering cartilage absorption via inducing the generation of regulatory T cells

摘要

The objective of the present study was to explore the mechanisms of transforming growth factor (TGF)-1 inhibiting the absorption of tissue engineering cartilage. We transfected TGF-1 gene into bone marrow mesenchymal stem cells (BMMSCs) and co-cultured with interferon (IFN)- and tumour necrosis factor (TNF)- and CD4(+)CD25(-) T lymphocytes. We then characterized the morphological changes, apoptosis and characterization of chondrogenic-committed cells from TGF-1(+)BMMSCs and explored their mechanisms. Results showed that BMMSCs apoptosis and tissue engineering cartilage absorption in the group with added IFN- and TNF- were greater than in the control group. In contrast, there was little BMMSC apoptosis and absorption by tissue engineering cartilage in the group with added CD4(+)CD25(-) T lymphocytes; Foxp3(+)T cells and CD25(+)CD39(+) T cells were found. In contrast, no type II collagen or Foxp3(+)T cells or CD25(+)CD39(+) T cells was found in the TGF-1(-)BMMSC group. The data suggest that IFN- and TNF- induced BMMSCs apoptosis and absorption of tissue engineering cartilage, but the newborn regulatory T (Treg) cells inhibited the function of IFN- and TNF- and protected BMMSCs and tissue engineering cartilage. TGF-1not only played a cartilage inductive role, but also inhibited the absorption of tissue engineering cartilage. The pathway proposed in our study may simulate the actual reaction procedure after implantation of BMMSCs and tissue engineering cartilage in vivo. Copyright (c) 2013 John Wiley & Sons, Ltd.