Heart and Vascular Center, Semmelweis University, Budapest, H1122, Hungary.
National Heart and Lung Institute, Imperial College London, W12 0NN, United Kingdom.
Theranostics. 2022 Jun 6;12(10):4684-4702. doi: 10.7150/thno.69938. eCollection 2022.
Human induced pluripotent stem cell-derived endothelial cells can be candidates for engineering therapeutic vascular grafts. Here, we studied the role of three-dimensional culture on their characteristics and function both and . We found that differentiated hPSC-EC can re-populate decellularized biomatrices; they remain viable, undergo maturation and arterial/venous specification. Human PSC-EC develop antifibrotic, vasoactive and anti-inflammatory properties during recellularization. , a robust increase in perfusion was detected at the engraftment sites after subcutaneous implantation of an hPSC-EC-laden hydrogel in rats. Histology confirmed survival and formation of capillary-like structures, suggesting the incorporation of hPSC-EC into host microvasculature. In a canine model, hiPSC-EC-seeded onto decellularised vascular segments were functional as aortic grafts. Similarly, we showed the retention and maturation of hiPSC-EC and dynamic remodelling of the vessel wall with good maintenance of vascular patency. A combination of hPSC-EC and biomatrices may be a promising approach to repair ischemic tissues.
人诱导多能干细胞衍生的内皮细胞可以作为工程治疗性血管移植物的候选物。在这里,我们研究了三维培养对其特性和功能的影响。我们发现,分化的 hPSC-EC 可以重新填充脱细胞生物基质;它们保持存活、成熟并具有动脉/静脉特异性。在再细胞化过程中,人 PSC-EC 表现出抗纤维化、血管活性和抗炎特性。,在大鼠皮下植入负载 hPSC-EC 的水凝胶后,在植入部位检测到灌注明显增加。组织学证实了 hPSC-EC 的存活和毛细血管样结构的形成,表明 hPSC-EC 已整合到宿主微血管中。在犬模型中,种植在脱细胞血管段上的 hiPSC-EC 作为主动脉移植物具有功能。同样,我们表明 hiPSC-EC 的保留和成熟以及血管壁的动态重塑,保持了血管通畅性。hPSC-EC 和生物基质的结合可能是修复缺血组织的一种有前途的方法。