Endothelial progenitor cell-seeded grafts: rash and risky

Abstract

The patency of prosthetic vascular grafts is impaired by intimal hyperplasia (IH) near the anastomotic regions. The absence of a functional endothelial monolayer on the prosthetic grafts is an important stimulus for IH. To improve the outcome of synthetic vascular bypass surgery, cell seeding is a promising concept that has been extensively investigated and is still evolving. In the present paper, the concept of prosthetic graft cell seeding is discussed, with emphasis on its newest era: seeding with endothelial progenitor cells. Although experimental studies on prosthetic graft seeding using endothelial progenitor cells have shown excellent results on graft endothelialization, none of these studies reported favourable effects on the more clinically relevant end points such as IH or graft patency.

Figure 1

Potential mechanisms of protective effects of seeded endothelial cells (ECs) on intimal hyperplasia in vascular prosthesis. First, the production of nitric oxide (NO), C-type natriuretic peptide (CNP) and heparan sulphate (HS) by ECs leads to inhibiton of profileration and migration of vascular smooth muscle cells (VSMCs). Second, the production of NO and prostacyclin (PGI₂) by ECs inhibits platelet aggregation, with subsequent reduction in release of platelet-derived growth factor (PDGF) and thromboxane A2 (TxA2) by platelets. Third, the mechanical barrier formed by ECs prevents infiltration of leukocytes, thereby reducing the production of growth-stimulation cytokines including tumour necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β). + Stimulatory effect;− Inhibitory effect

Figure 2

Representative sections obtained at four weeks after arteri-ovenous graft implantation in pigs. Enhanced endothelialization in the anti-CD34-coated grafts coincided with profound increase in intimal hyperplasia at the venous anastomosis. Lectin-stained sections of bare (A) and CD34-coated grafts (B) obtained from the centre of the graft. Lectin is a marker for endothelial cells. Elastin von Gieson-stained sections of the venous anastomosis of bare grafts (C) and CD34-coated grafts (D). Reproduced from reference with permission