Rütsche Dominic, Nanni Monica, Cheng Phil, Caflisch Nicolà, Tastanova Aizhan, Jenni Céline, Levesque Mitchell P, Moehrlen Ueli, Klar Agnes S, Biedermann Thomas
Tissue Biology Research Unit, Department of Surgery, University Children's Hospital Zurich, Lenggstrasse 30, Zurich, 8008, Switzerland.
Children's Research Center, University Children's Hospital Zurich, Lenggstrasse 30, Zurich, 8008, Switzerland.
Small Methods. 2025 Jan 28:e2401588. doi: 10.1002/smtd.202401588.
The bioengineering of vascular networks is pivotal to create 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, scRNA-seq is first employed to investigate the arterio-venous endothelial cell marker patterning in human fetal and juvenile skin. Transcriptomic analysis reveals that arterial and venous endothelial cell markers NRP1 (neuropilin 1) and NR2F2 (nuclear receptor subfamily 2 group F member 2) are broadly expressed in fetal and juvenile skin. In contrast, expression of NRP1 and NR2F2 on the protein level is cell-type specific and is retained in 2D (2-dimensional) cultures in vitro. Finally, distinct arterial and venous capillaries are bioengineered in 3D (3-dimensional) hydrogels and rapid anastomosis is demonstrated with the host vasculature in vivo. In summary, the bioengineering of human arterial, venous, and lymphatic capillaries is established, hence paving the way for these cells to be used in regenerative medicine and future clinical applications.
血管网络的生物工程对于为再生医学应用创建复杂组织和器官至关重要。然而，包含动脉和静脉丛以及淋巴管网络的生物工程组织尚未得到探索。在此，首次采用单细胞RNA测序（scRNA-seq）来研究人类胎儿和青少年皮肤中的动静脉内皮细胞标记模式。转录组分析表明，动脉和静脉内皮细胞标记物神经纤毛蛋白1（NRP1）和核受体亚家族2组F成员2（NR2F2）在胎儿和青少年皮肤中广泛表达。相比之下，NRP1和NR2F2在蛋白质水平上的表达具有细胞类型特异性，并在体外二维（2D）培养中得以保留。最后，在三维（3D）水凝胶中对不同的动脉和静脉毛细血管进行了生物工程构建，并在体内证明了其与宿主脉管系统的快速吻合。总之，人类动脉、静脉和淋巴管的生物工程构建得以实现，从而为这些细胞在再生医学和未来临床应用中的使用铺平了道路。
