Tissue-engineered vascular grafts transform into mature blood vessels via an inflammation-mediated process of vascular remodeling

TLDR

Biodegradable scaffolds seeded with bone marrow mononuclear cells are the earliest tissue‑engineered vascular grafts used clinically, and they transform into living blood vessels lined by endothelial cells and smooth muscle cells, yet the underlying mechanism remains unclear. The study aimed to determine whether the seeded bone marrow mononuclear cells differentiate into mature vascular cells of the neovessel. This was tested by implanting human BMC‑seeded biodegradable scaffolds into immunodeficient mice as venous interposition grafts. In mice, the grafts gradually became living blood vessels over six months; seeded human BMCs disappeared within days, while mouse monocytes, smooth muscle cells, and endothelial cells repopulated the scaffold, with BMCs secreting monocyte chemoattractant protein‑1 and enhancing early monocyte recruitment, indicating that TEVG transformation occurs via an inflammatory remodeling process.

Abstract

Biodegradable scaffolds seeded with bone marrow mononuclear cells (BMCs) are the earliest tissue-engineered vascular grafts (TEVGs) to be used clinically. These TEVGs transform into living blood vessels in vivo, with an endothelial cell (EC) lining invested by smooth muscle cells (SMCs); however, the process by which this occurs is unclear. To test if the seeded BMCs differentiate into the mature vascular cells of the neovessel, we implanted an immunodeficient mouse recipient with human BMC (hBMC)-seeded scaffolds. As in humans, TEVGs implanted in a mouse host as venous interposition grafts gradually transformed into living blood vessels over a 6-month time course. Seeded hBMCs, however, were no longer detectable within a few days of implantation. Instead, scaffolds were initially repopulated by mouse monocytes and subsequently repopulated by mouse SMCs and ECs. Seeded BMCs secreted significant amounts of monocyte chemoattractant protein-1 and increased early monocyte recruitment. These findings suggest TEVGs transform into functional neovessels via an inflammatory process of vascular remodeling.