Pericyte-based human tissue engineered vascular grafts

Abstract

The success of small-diameter tissue engineered vascular grafts (TEVGs) greatly relies on an appropriate cell source and an efficient cellular delivery and carrier system. Pericytes have recently been shown to express mesenchymal stem cell features. Their relative availability and multipotentiality make them a promising candidate for TEVG applications. The objective of this study was to incorporate pericytes into a biodegradable scaffold rapidly, densely and efficiently, and to assess the efficacy of the pericyte-seeded scaffold in vivo. Bi-layered elastomeric poly(ester-urethane)urea scaffolds (length=10mm; inner diameter=1.3mm) were bulk seeded with 3×106 pericytes using a customized rotational vacuum seeding device in less than 2 min (seeding efficiency > 90%). The seeded scaffolds were cultured in spinner flasks for 2 days and then implanted into Lewis rats as aortic interposition grafts for 8 weeks. Results showed pericytes populated the porous layer of the scaffolds evenly and maintained their original phenotype after the dynamic culture. After implantation, pericyte-seeded TEVGs showed a significant higher patency rate than the unseeded control: 100% versus 38% (p < 0.05). Patent pericyte-seeded TEVGs revealed extensive tissue remodeling with collagen and elastin present. The remodeled tissue consisted of multiple layers of α-smooth muscle actin- and calponin-positive cells, and a von Willebrand factor-positive monolayer in the lumen. These results demonstrate the feasibility of a pericyte-based TEVG and suggest that the pericytes play a role in maintaining patency of the TEVG as an arterial conduit.

Pericytes, mesenchymal stem cells and their contributions to tissue repair

“…Despite an intact immune system, implants were not rejected, supporting the notion that MSCderived implants are less immunogenic, perhaps due to the secretion of anti-inflammatory factors (He et al, 2010). It was suggested that pericytes reduce obstruction in vascular grafts and show promise for use in arterial conduits (He et al, 2010).…”

“…Cultured flow cytometry-sorted pericytes from human skeletal tissue (CD146/NG2/PDGFRβ+, CD45/CD56/CD34-) seeded onto poly(esterurethane) urea (PEUU) scaffolds have been used to create small-diameter tissue engineered vascular grafts (TEVG) (He et al, 2010). Following implantation, TEVG displayed vascular remodelling as evidenced by collagen and elastin deposition, as well as the presence of αSMA and calponin (He et al, 2010).…”

“…It was suggested that pericytes reduce obstruction in vascular grafts and show promise for use in arterial conduits (He et al, 2010). Of concern however, the grafts did not seem to fully integrate with the host, as the majority of the tissue was rat-derived, rather than humanderived.…”

Dedifferentiated fat cells: an alternative source of adult multipotent cells from the adipose tissues

“…Our novel findings above on the perivascular behavior of DFAT cells were consistent to the new understandings of MSCs. Recent studies identified that pericytes in multiple organs and tissues could demonstrate perivascular markers (CD146, NG2 and CD140b) and MSCs markers (CD44, CD73, CD90, CD105), exhibiting osteogenic, chondrogenic and adipogenic potentials [55][56][57]. MSCs within adult mesenchymal tissues such as bone and adipose also could differentiate into or act as pericytes without induction of growth factors [58][59].…”

Nano-ceramic Composite Scaffolds for Bioreactor-based Bone Engineering

“…With static culture techniques, the transportation of oxygen, nutrients, and low-molecular-weight metabolites is limited by diffusion preventing cells from being able to survive in the scaffold interior. To overcome this problem, a variety of dynamic culture systems have been used including perfusion bioreactors [45,56], spinner flasks [32,58], roller bottles [26], and rotating wall bioreactors [55,59]. The high-aspect ratio vessel (HARV) bioreactor is a low-shear, high-mass transfer system that improves cell-seeded bone tissue-engineering scaffold performance [6,9,60].…”