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Human dermal microvascular arterial and venous blood endothelial cells and their use in bioengineered dermo-epidermal skin substitutes in vitro and in vivo

Rütsche, Dominic1; Nanni, Monica1; Cheng, Phil2; Caflisch, Nicolà1; Tastanova, Aizhan2; Jenni, Céline1; Levesque, Mitchell2; Moehrlen, Ueli1; Klar, Agnes1; Biedermann, Thomas1

Research facility: University Children's Hospital Zurich
Published Aug 05, 2024 on Dryad. https://doi.org/10.5061/dryad.mcvdnck85

Data files

Aug 05, 2024 version files 105.55 MB

Abstract

The bioengineering of vascular networks is pivotal to creating complex tissues and organs for regenerative medicine applications. However, bioengineered tissues comprising an arterial and venous plexus alongside a lymphatic capillary network have not been explored yet. Here, we first employed scRNA-seq to investigate the arterio-venous endothelial cell marker patterning in human fetal and juvenile skin. Transcriptomic analysis revealed that arterial and venous endothelial cell markers NRP1 and NR2F2 are broadly expressed in fetal and juvenile skin. In contrast, expression of NRP1 and NR2F2 on the protein level was cell-type specific and was retained in 2D cultures in vitro. Finally, we bioengineered distinct arterial and venous capillaries in 3D hydrogels and demonstrated rapid anastomosis with the host vasculature in vivo. In summary, we established the bioengineering of human arterial, venous, and lymphatic capillaries, hence paving the way for these cells to be used in regenerative medicine and future clinical applications.