Engineering vascularized flaps using adipose-derived microvascular endothelial cells and mesenchymal stem cells

Abstract

Human adipose-derived microvascular endothelial cells (HAMEC) and mesenchymal stem cells (MSC) have been shown to bear angiogenic and vasculogenic capabilities. We hypothesize that co-culturing HAMEC:MSC on a porous biodegradable scaffold in vitro, later implanted as a graft around femoral blood vessels in a rat, will result in its vascularization by host vessels, creating a functional vascular flap that can effectively treat a range of large full-thickness soft tissue defects.HAMEC were co-cultured with MSC on polymeric three-dimensional porous constructs. Grafts were then implanted around the femoral vessels of a rat. To ensure vessel sprouting from the main femoral vessels, grafts were pre-isolated from the surrounding tissue. Graft vascularization was monitored to confirm full vascularization before flap transfer. Flaps were then transferred to treat both abdominal wall and exposed bone and tendon of an ankle defects. Flaps were analysed to determine vascular properties in terms of maturity, functionality and survival of implanted cells. Findings show that pre-isolated grafts bearing the HAMEC:MSC combination promoted formation of highly vascularized flaps, which were better integrated in both defect models. The results of this study show the essentiality of a specific adipose-derived cell combination in successful graft vascularization and integration, two processes crucial for flap survival. Copyright

Bioprinting of high cell‐density constructs leads to controlled lumen formation with self‐assembly of endothelial cells

“…Bioprinting technology allows to address this vascularization challenge with some innovative approaches. Endothelial cells (ECs) from different sources, such as primary human umbilical vein endothelial cells (HUVECs), primary human dermal microvascular endothelial cells (HDMECs), or stem cell-derived ECs, have therefore been used as cellular building blocks for the fabrication of vascularization precursors in many forms (Alajati et al, 2008;Freiman et al, 2017;Heiss et al, 2015;Jain, Au, Tam, Duda, & Fukumura, 2005;Laschke & Menger, 2017).…”

Uncultivated stromal vascular fraction is equivalent to adipose‐derived stem and stromal cells on porous polyurethrane scaffolds forming adipose tissue in vivo

“…Therefore, almost all implanted cells must have been degraded to the time point of histological evaluation. Taken together, we assume that the formation of adipose tissue and the neovascularization is more likely attributable to mediators, secreted by seeded ASCs and SVF cells . These agents might, for example, be IGF, VEGF, bFGF, and HGF …”

“…Taken together, we assume that the formation of adipose tissue and the neovascularization is more likely attributable to mediators, secreted by seeded ASCs and SVF cells. 19,22,43,44 These agents might, for example, be IGF, VEGF, bFGF, and HGF. 28,45 In a clinical setting, both mechanisms of tissue formation, namely either the mediated migration of host cells to the scaffold or the differentiation of implanted cells, would go hand in hand, as autologous transplantation of SVF cells is desirable.…”

Enhanced Host Neovascularization of Prevascularized Engineered Muscle Following Transplantation into Immunocompetent versus Immunocompromised Mice

“…While much progress has been made in the field of tissue engineering, most studies utilize immunocompromised animal models or administer immunosuppressive therapy to study the integration and survival of human engineered tissues in animals [8][9][10][11][12][13][14]. These works have established that in vitro graft prevascularization by human vascular cells is beneficial for graft integration and neovascularization post-implantation [8][9][10]13,[15][16][17]. It was also shown that culturing human vascular cells on biodegradable and biocompatible poly (l-lactic acid)/poly (lactide-co-glycolic acid) (PLLA/PLGA) scaffolds combined with fibrin gel results in the spontaneous formation of vessel-like structures in vitro, which later anastomose with the host vasculature upon transplantation into immunocompromised animals [9,16,18].…”