Human skin is a highly vascularised organ, where blood vessels perform essential roles in maintaining skin homeostasis. Autologous skin graft transplantation is considered to be the gold standard approach for treating cutaneous burns. Although autologous skin grafts are effective in supporting wound closure, their therapeutic benefits are limited by fragility, abnormal pigmentation, lack of hair, and lack of sensation. Specifically, cultured epithelial autografts demonstrate poor infection tolerance due to inferior vascular perfusion, as they only close the epidermal barrier. These limitations highlight the importance of developing vascularised skin substitutes as they can mitigate infection and necrosis. Currently, there is an unmet challenge to generate vascularised, functional skin organoids. Here, we demonstrate our vascularised model of human skin organoids derived from induced pluripotent stem cells.
With our novel co-culture technique, we were able to vascularise human skin organoids and recapitulate a physiologically relevant environment. Using immunofluorescence microscopy and flow cytometric analyses, we observed a heterogenous population of: endothelial, mural, and mesenchymal stem cells integrate with the dermis and hair follicles of skin organoids. The distinct separation of vasculature from the epidermis recapitulates the architecture of vascularised human skin. Furthermore, skin organoids lack skin-resident immune cells. With our vascularised model, we observed immune cells integrate within the dermal and epidermal layers of the skin organoids.
Consequently, we established a vascularised human skin organoid model with immune cells that is arguably a more physiologically relevant in vitro model of human skin, compared to current skin organoid models. Vascularised skin organoids demonstrate significant translational potential as they can be used to investigate the role of vasculature in human skin, with the capacity to further current wound healing capabilities.