Park Jinkyu, Riaz Muhammad, Qin Lingfeng, Zhang Wei, Batty Luke, Fooladi Saba, Kural Mehmet H, Li Xin, Luo Hangqi, Xu Zhen, Wang Juan, Banno Kimihiko, Gu Sean X, Yuan Yifan, Anderson Christopher W, Ellis Matthew W, Zhou Jiahui, Luo Jiesi, Shi Xiangyu, Shin Jae Hun, Liu Yufeng, Lee Seoyeon, Yoder Mervin C, Elder Robert W, Mak Michael, Thorn Stephanie, Sinusas Albert, Gruber Peter J, Hwa John, Tellides George, Niklason Laura E, Qyang Yibing
Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06511, USA; Yale Stem Cell Center, New Haven, CT 06520, USA; Department of Physiology, College of Medicine, Hallym University, Hallymdaehak-gil, Chuncheon-si 24252, Gangwon-Do, South Korea.
Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06511, USA; Yale Stem Cell Center, New Haven, CT 06520, USA.
Cell Stem Cell. 2025 Jan 2;32(1):137-143.e6. doi: 10.1016/j.stem.2024.11.006. Epub 2024 Dec 6.
Tissue-engineered vascular conduits (TEVCs), often made by seeding autologous bone marrow cells onto biodegradable polymeric scaffolds, hold promise toward treating single-ventricle congenital heart defects (SVCHDs). However, the clinical adoption of TEVCs has been hindered by a high incidence of graft stenosis in prior TEVC clinical trials. Herein, we developed endothelialized TEVCs by coating the luminal surface of decellularized human umbilical arteries with human induced pluripotent stem cell (hiPSC)-derived endothelial cells (ECs), followed by shear stress training, in flow bioreactors. These TEVCs provided immediate antithrombotic function and expedited host EC recruitment after implantation as interposition inferior vena cava grafts in nude rats. Graft patency was maintained with no thrombus formation, followed by complete replacement of host ECs. Our study lays the foundation for future production of fully biologic TEVCs composed of hiPSC-derived ECs as an innovative therapy for SVCHDs.
组织工程血管移植物(TEVCs)通常是通过将自体骨髓细胞接种到可生物降解的聚合物支架上制成的,有望用于治疗单心室先天性心脏缺陷(SVCHDs)。然而,在先前的TEVC临床试验中,移植物狭窄的高发生率阻碍了TEVCs在临床上的应用。在此,我们通过在脱细胞人脐动脉的管腔表面涂上人诱导多能干细胞(hiPSC)衍生的内皮细胞(ECs),然后在流动生物反应器中进行剪切应力训练,开发出了内皮化的TEVCs。这些TEVCs在植入后作为裸鼠下腔静脉间置移植物时,提供了即时的抗血栓功能,并加快了宿主EC的募集。移植物保持通畅,无血栓形成,随后宿主EC被完全替代。我们的研究为未来生产由hiPSC衍生的ECs组成的完全生物性TEVCs奠定了基础,作为一种治疗SVCHDs的创新疗法。