The innate immune system contributes to tissue-engineered vascular graft performance

Area of Science:

• Biomedical Engineering
• Immunology
• Vascular Surgery

Background:

• Stenosis is a primary cause of tissue-engineered vascular graft (TEVG) failure in clinical trials.
• The role of the host immune response in TEVG stenosis remains incompletely understood.

Purpose of the Study:

• To investigate the contribution of the host immune response to TEVG stenosis using a murine model.
• To identify specific immune components involved in TEVG-induced stenosis.

Main Methods:

• Comparison of TEVG stenosis in wild-type (WT), severe combined immunodeficient (SCID), and SCID/beige (bg) mice.
• Assessment of stenosis severity by luminal diameter measurements.
• Evaluation of the impact of NK cell neutralization and antiplatelet therapy on TEVG patency.
• Analysis of macrophage infiltration and pro-inflammatory cytokine expression in TEVG explants.

Main Results:

• WT mice exhibited significant stenosis, while SCID/beige mice showed dramatically reduced stenosis.
• SCID mice, lacking adaptive immunity, displayed stenosis rates comparable to WT controls.
• NK cell neutralization and antiplatelet therapy partially improved TEVG patency in WT mice.
• SCID/bg mice demonstrated a blunted immune response, with reduced macrophage infiltration and pro-inflammatory cytokine expression.

Conclusions:

• The innate immune response, involving NK cells and platelets, plays a critical role in TEVG stenosis.
• Targeting innate immunity may offer a therapeutic strategy for improving the patency of next-generation TEVGs.