Tumor necrosis factor-α inhibition restores matrix formation by human adipose-derived stem cells in the late stage of chondrogenic differentiation

BACKGROUND

Cartilage tissue engineering is a promising strategy for treating cartilage damage. Matrix formation by adipose-derived stem cells (ADSCs), which are one type of seed cell used for cartilage tissue engineering, decreases in the late stage of induced chondrogenic differentiation in vitro, which seriously limits research on ADSCs and their application.

AIM

To improve the chondrogenic differentiation efficiency of ADSCs in vitro, and optimize the existing chondrogenic induction protocol.

METHODS

Tumor necrosis factor-alpha (TNF-α) inhibitor was added to chondrogenic culture medium, and then Western blotting, enzyme linked immunosorbent assay, immunofluorescence and toluidine blue staining were used to detect the cartilage matrix secretion and the expression of key proteins of nuclear factor kappa-B (NF-κB) signaling pathway.

RESULTS

In this study, we found that the levels of TNF-α and matrix metalloproteinase 3 were increased during the chondrogenic differentiation of ADSCs. TNF-α then bound to its receptor and activated the NF-κB pathway, leading to a decrease in cartilage matrix synthesis and secretion. Blocking TNF-α with its inhibitors etanercept (1 μg/mL) or infliximab (10 μg/mL) significantly restored matrix formation.

CONCLUSION

Therefore, this study developed a combination of ADSC therapy and targeted anti-inflammatory drugs to optimize the chondrogenesis of ADSCs, and this approach could be very beneficial for translating ADSC-based approaches to treat cartilage damage.

Key Words: Adipose-derived mesenchymal stem cells, Human adipose-derived mesenchymal stem cells, Chondrogenic differentiation, Tumor necrosis factor-alpha, Etanercept, Infliximab, Nuclear factor kappa-B

Core Tip: Adipose stem cells are important seed cells that are used in cartilage tissue engineering. However, at present, cartilage matrix secretion by adipose-derived stem cells (ADSCs) inevitably decreases during the late stage of induced chondrogenic differentiation in vitro, which seriously limits the further application of ADSCs. Our team found that the level of inflammation in the culture system, mainly the levels of tumor necrosis factor-alpha (TNF-α) and matrix metalloproteinase 3, continuously increased during the chondrogenic differentiation of ADSCs. To address this issue, our team added etanercept or infliximab, which are targeted inhibitors of TNF-α, to the chondrogenic differentiation induction medium and successfully restored matrix formation by human ADSCs in the late stage of chondrogenic differentiation. Further studies found that these effects were achieved by reducing NF-κB pathway activation.

• Citation: Wan JT, Qiu XS, Fu ZH, Huang YC, Min SX. Tumor necrosis factor-α inhibition restores matrix formation by human adipose-derived stem cells in the late stage of chondrogenic differentiation. World J Stem Cells 2022; 14(11): 798-814
• URL: https://www.wjgnet.com/1948-0210/full/v14/i11/798.htm
• DOI: https://dx.doi.org/10.4252/wjsc.v14.i11.798