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Cell stem cell. 2025 Jan 2;32(1):137-143.e6. doi: 10.1016/j.stem.2024.11.006 Q120.42025

Fully biologic endothelialized-tissue-engineered vascular conduits provide antithrombotic function and graft patency

完全的生物工程化的血管移植物可提供抗凝和搭桥血流通畅的功能 翻译改进

Jinkyu Park  1, Muhammad Riaz  2, Lingfeng Qin  3, Wei Zhang  2, Luke Batty  4, Saba Fooladi  2, Mehmet H Kural  5, Xin Li  2, Hangqi Luo  2, Zhen Xu  2, Juan Wang  5, Kimihiko Banno  6, Sean X Gu  7, Yifan Yuan  5, Christopher W Anderson  4, Matthew W Ellis  8, Jiahui Zhou  2, Jiesi Luo  2, Xiangyu Shi  2, Jae Hun Shin  9, Yufeng Liu  10, Seoyeon Lee  11, Mervin C Yoder  6, Robert W Elder  12, Michael Mak  13, Stephanie Thorn  14, Albert Sinusas  14, Peter J Gruber  15, John Hwa  14, George Tellides  16, Laura E Niklason  17, Yibing Qyang  18

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作者单位

  • 1 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.
  • 2 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.
  • 3 Department of Surgery, Yale University, New Haven, CT 06520, USA.
  • 4 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 Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
  • 5 Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Anesthesiology, Yale University, New Haven, CT 06519, USA.
  • 6 Indiana Center for Regenerative Medicine and Engineering, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
  • 7 Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06511, USA; Department of Laboratory Medicine, Yale University, New Haven, CT 06519, USA.
  • 8 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 Cellular and Molecular Physiology, Yale University, New Haven, CT 06519, USA.
  • 9 Department of Internal Medicine, Section of Endocrinology and Metabolism, Yale University School of Medicine, New Haven, CT 06520, USA.
  • 10 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; Yale Biological and Biomedical Sciences, Graduate School of Arts and Sciences, Yale University, New Haven, CT 06511, USA.
  • 11 Yale Biological and Biomedical Sciences, Graduate School of Arts and Sciences, Yale University, New Haven, CT 06511, USA.
  • 12 Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06511, USA; Department of Pediatrics, Yale School of Medicine, New Haven, CT 06520, USA.
  • 13 Department of Biomedical Engineering, Yale University, New Haven, CT 06519, USA.
  • 14 Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06511, USA; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA.
  • 15 Department of Surgery, Yale University, New Haven, CT 06520, USA; Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
  • 16 Department of Surgery, Yale University, New Haven, CT 06520, USA; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA.
  • 17 Yale Stem Cell Center, New Haven, CT 06520, USA; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Anesthesiology, Yale University, New Haven, CT 06519, USA; Department of Biomedical Engineering, Yale University, New Haven, CT 06519, USA.
  • 18 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 Pathology, Yale School of Medicine, New Haven, CT 06520, USA; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Biomedical Engineering, Yale University, New Haven, CT 06519, USA. Electronic address: yibing.qyang@yale.edu.

    • DOI: 10.1016/j.stem.2024.11.006 PMID: 39644899

    摘要 中英对照阅读

    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.

    Keywords: endothelial cell; flow bioreactor; human induced pluripotent stem cell; shear stress training; single ventricle congenital heart defect; tissue-engineered vascular conduit.

    Keywords：antithrombotic function; endothelialization

    组织工程血管移植物（TEVCs）通常通过将自体骨髓细胞接种到可降解的聚合物支架上来制造，有望用于治疗单心室先天性心脏缺陷（SVCHDs）。然而，在之前的TEVC临床试验中，移植狭窄的发生率较高，这阻碍了TEVC在临床上的应用。在此，我们开发了一种内皮化的TEVC，通过将人诱导多能干细胞（hiPSC）衍生的内皮细胞（ECs）涂覆于脱细胞的人脐动脉管腔表面，并经过流体生物反应器中的剪切应力训练来实现。这些TEVC在裸鼠中作为下腔静脉移植移植物植入后，提供了即时的抗血栓功能并加快了宿主EC的招募。移植物保持通畅无血栓形成，并最终完全被宿主EC替代。我们的研究为未来制造由hiPSC衍生的EC组成的全生物TEVCs以创新治疗SVCHDs奠定了基础。

    关键词：内皮细胞；流体生物反应器；人诱导多能干细胞；剪切应力训练；单心室先天性心脏缺陷；组织工程血管移植物。

    关键词：组织工程血管移植物; 抗凝血功能; 内皮化

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    期刊名：Cell stem cell

    缩写：CELL STEM CELL

    ISSN：1934-5909

    e-ISSN：1875-9777

    IF/分区：20.4/Q1

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    Fully biologic endothelialized-tissue-engineered vascular conduits provide antithrombotic function and graft patency