There is a clinical need for better blood vessel substitutes, as current surgical procedures are limited by the availability of suitable autologous vessels and suboptimal behavior of synthetic grafts in small caliber arterial graft (<5  mm) applications. The aim of the present study was to compare the mechanical properties of arterial and venous tissue-engineered vascular constructs produced by the self-assembly approach using cells extracted from either the artery or vein harvested from the same human umbilical cord. The production of a vascular construct comprised of a media and an adventitia (TEVMA) was achieved by rolling a continuous tissue sheet containing both smooth muscle cells and adventitial fibroblasts grown contiguously in the same tissue culture plate. Histology and immunofluorescence staining were used to evaluate the structure and composition of the extracellular matrix of the vascular constructs. The mechanical strength was assessed by uniaxial tensile testing, whereas viscoelastic behavior was evaluated by stepwise stress-relaxation and by cyclic loading hysteresis analysis. Tensile testing showed that the use of arterial cells resulted in stronger and stiffer constructs when compared with those produced using venous cells. Moreover, cyclic loading demonstrated that constructs produced using arterial cells were able to bear higher loads for the same amount of strain when compared with venous constructs. These results indicate that cells isolated from umbilical cord can be used to produce vascular constructs. Arterial constructs possessed superior mechanical properties when compared with venous constructs produced using cells isolated from the same human donor. This study highlights the fact that smooth muscle cells and fibroblasts originating from different cell sources can potentially lead to distinct tissue properties when used in tissue engineering applications.

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The human umbilical cord (UC) has attracted interest as a source of cells for many research applications. UC solid tissues contain four cell types: epithelial, stromal, smooth muscle and endothelial cells. We have developed a unique protocol for the sequential extraction of all four cell types from a single UC, allowing tissue reconstruction using multiple cell types from the same source. By combining perfusion, immersion and explant techniques, all four cell types have been successfully expanded in monolayer cultures. We have also characterised epithelial and Wharton’s jelly cells (WJC) by immunolabelling of specific proteins. Epithelial cell yields averaged at 2.3 × 10⁵ cells per centimetre UC, and the cells expressed an unusual combination of keratins typical of simple, mucous and stratified epithelia. Stromal cells in the Wharton’s jelly expressed desmin, α-smooth muscle actin, elastin, keratins (K12, K16, K18 and K19), vimentin and collagens. Expression patterns in cultured cells resembled those found in situ except for basement membrane components and type III collagen. These stromal cells featured a sustained proliferation rate up to passage 12 after thawing. The mesenchymal stem cell (MSC) character of the WJC was confirmed by their expression of typical MSC surface markers and by adipogenic and osteogenic differentiation assays. To emphasise and demonstrate their potential for regenerative medicine, UC cell types were successfully used to produce human tissue-engineered constructs. Both bilayered stromal/epithelial and vascular substitutes were produced, establishing the versatility and importance of these cells for research and therapeutic applications.

Radiotherapy for cancer treatment is often associated with skin damage that can lead to incapacitating hard-to-heal wounds. No permanent curative treatment has been identified for radiodermatitis. This study provides a detailed characterization of the dose-dependent impact of ionizing radiation on skin cells (45, 60, or 80 grays). We evaluated both early and late effects on murine dorsal skin with a focus on the healing process after two types of surgical challenge. The irradiated skin showed moderate to severe damage increasing with the dose. Four weeks after irradiation, the epidermis featured increased proliferation status while the dermis was hypovascular with abundant α-SMA intracellular expression. Excisional wounds created on these tissues exhibited delayed global wound closure. To assess potential long-lasting side effects of irradiation, radiodermatitis features were followed until macroscopic healing was notable (over 8 to 22 weeks depending on the dose), at which time incisional wounds were made. Severity scores and biomechanical analyses of the scar tissues revealed that seemingly healed irradiated skin still displayed altered functionality. Our detailed investigation of both the acute and chronic repercussions of radiotherapy on skin healing provides a relevant new in vivo model that will instruct future studies evaluating the efficacy of new treatments for radiodermatitis.

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