Small-Diameter Blood Vessels Engineered With Bone Marrow–Derived Cells

TLDR

Bone marrow–derived cells can differentiate into endothelial‑like and smooth muscle‑like cells, making them a promising alternative cell source for vascular tissue engineering. This study aimed to determine whether BMCs can regenerate vascular tissues and enhance patency in tissue‑engineered small‑diameter (3 mm) vascular grafts. The authors fabricated 3 mm decellularized canine carotid grafts, seeded them with in‑vitro differentiated BMCs, implanted them in donor dogs, and evaluated vascular‑tissue regeneration and patency by immunohistochemistry and angiography. BMC‑seeded grafts stayed patent for up to 8 weeks, regenerated endothelium, media, and adventitia, and retained fluorescently labeled BMCs, demonstrating that BMCs can regenerate vascular tissues and improve graft patency—a first report of a small‑diameter neovessel engineered with BMCs.

Abstract

In Brief Objective: The objective of this study is to investigate if bone marrow–derived cells (BMCs) regenerate vascular tissues and improve patency in tissue-engineered small-diameter (internal diameter = 3 mm) vascular grafts. Summary Background Data: BMCs have demonstrated the ability to differentiate into endothelial-like cells and vascular smooth muscle–like cells and may offer an alternative cell source for vascular tissue engineering. Thus, we tissue-engineered small-diameter vascular grafts with BMCs and decellularized arteries. Methods: Canine BMCs were differentiated in vitro into smooth muscle α-actin/smooth muscle myosin heavy-chain-positive cells and von Willebrand factor/CD31-positive cells and seeded onto decellularized canine carotid arteries (internal diameter = 3 mm). The seeded grafts were implanted in cell donor dogs. The vascular-tissue regeneration and graft patency were investigated with immunohistochemistry and angiography, respectively. Results: The vascular grafts seeded with BMCs remained patent for up to 8 weeks in the canine carotid artery interposition model, whereas nonseeded grafts occluded within 2 weeks. Within 8 weeks after implantation, the vascular grafts showed regeneration of the 3 elements of artery (endothelium, media, and adventitia). BMCs labeled with a fluorescent dye prior to implantation were detected in the retrieved vascular grafts, indicating that the BMCs participated in the vascular tissue regeneration. Conclusions: Here we show that BMCs have the potential to regenerate vascular tissues and improve patency in tissue-engineered small-diameter vascular grafts. This is the first report of a small-diameter neovessel engineered with BMCs as a cell source. The small-diameter (internal diameter = 3 mm) vascular grafts were tissue-engineered with autologous bone marrow–derived cells (BMCs) and decellularized matrices. Canine BMCs were induced to differentiate in vitro into endothelial-like cells and smooth muscle–like cells. The BMCs seeding on vascular grafts improved the patency and regenerated vascular tissues in canine models. This study suggests the possibility of using BMCs as an alternative cell source for tissue engineering of small-diameter vascular grafts.