Monocyte Recruitment for Vascular Tissue Regeneration

A strategy to recruit monocytes (MCs) from blood to regenerate vascular tissue from unseeded (cell-free) tissue engineered vascular grafts is presented. When immobilized on the surface of vascular grafts, the fusion protein, H2R5 can capture blood-derived MC under static or flow conditions in a shear stress dependent manner. The bound MC turns into macrophages (M phi) expressing both M1 and M2 phenotype specific genes. When H2R5 functionalized acellular-tissue engineered vessels (A-TEVs) are implanted into the mouse aorta, they remain patent and form a continuous endothelium expressing both endothelial cell (EC) and MC specific proteins. Underneath the EC layer, multiple cells layers are formed coexpressing both smooth muscle cell (SMC) and MC specific markers. Lineage tracing analysis using a novel CX3CR1-confetti mouse model demonstrates that fluorescently labeled MC populates the graft lumen by two and four weeks postimplantation, providing direct evidence in support of MC/M phi recruitment to the graft lumen. Given their abundance in the blood, circulating MCs may be a great source of cells that contribute directly to the endothelialization and vascular wall formation of acellular vascular grafts under the right chemical and biomechanical cues.

Automated summary

A strategy to recruit monocytes (MCs) from blood to regenerate vascular tissue from unseeded tissue engineered vascular grafts is presented. The fusion protein, H2R5, can capture blood-derived MC under static or flow conditions on the surface of vascular grafts. This bound MC then transforms into macrophages (M phi) expressing specific genes. When these functionalized grafts are implanted, they form a continuous endothelium expressing specific proteins and multiple cell layers expressing specific markers. Lineage tracing analysis provides direct evidence of MC/M phi recruitment to the graft lumen. Circulating MCs may potentially contribute to the endothelialization and vascular wall formation of acellular vascular grafts.