Motta Sarah E, Zaytseva Polina, Fioretta Emanuela S, Lintas Valentina, Breymann Christian, Hoerstrup Simon P, Emmert Maximilian Y
Institute for Regenerative Medicine (IREM), University of Zurich, Zurich, Switzerland.
Wyss Translational Center Zurich, University and ETH Zurich, Zurich, Switzerland.
Front Bioeng Biotechnol. 2022 Mar 31;10:867877. doi: 10.3389/fbioe.2022.867877. eCollection 2022.
Hemocompatibility of cardiovascular implants represents a major clinical challenge and, to date, optimal antithrombotic properties are lacking. Next-generation tissue-engineered heart valves (TEHVs) made from human-cell-derived tissue-engineered extracellular matrices (hTEMs) demonstrated their recellularization capacity and may represent promising candidates to avoid antithrombotic therapy. To further enhance their hemocompatibility, we tested hTEMs pre-endothelialization potential using human-blood-derived endothelial-colony-forming cells (ECFCs) and umbilical vein cells (control), cultured under static and dynamic orbital conditions, with either FBS or hPL. ECFCs performance was assessed scratch assay, thereby recapitulating the surface damages occurring in transcatheter valves during crimping procedures. Our study demonstrated: feasibility to form a confluent and functional endothelium on hTEMs with expression of endothelium-specific markers; ECFCs migration and confluency restoration after crimping tests; hPL-induced formation of neo-microvessel-like structures; feasibility to pre-endothelialize hTEMs-based TEHVs and ECFCs retention on their surface after crimping. Our findings may stimulate new avenues towards next-generation pre-endothelialized implants with enhanced hemocompatibility, being beneficial for selected high-risk patients.
心血管植入物的血液相容性是一项重大的临床挑战，迄今为止，仍缺乏最佳的抗血栓性能。由人细胞衍生的组织工程细胞外基质（hTEMs）制成的下一代组织工程心脏瓣膜（TEHVs）已证明其再细胞化能力，可能是避免抗血栓治疗的有前途的候选者。为了进一步提高其血液相容性，我们使用人血来源的内皮集落形成细胞（ECFCs）和脐静脉细胞（对照），在静态和动态轨道条件下，分别添加胎牛血清（FBS）或人血小板裂解液（hPL），测试了hTEMs的预内皮化潜力。通过划痕试验评估ECFCs的性能，从而模拟经导管瓣膜在压接过程中发生的表面损伤。我们的研究表明：在hTEMs上形成融合且功能正常的内皮并表达内皮特异性标志物是可行的；压接试验后ECFCs的迁移和融合恢复；hPL诱导形成新的微血管样结构；预内皮化基于hTEMs的TEHVs是可行的，且压接后ECFCs能保留在其表面。我们的研究结果可能会为下一代具有更高血液相容性的预内皮化植入物开辟新途径，这对选定的高危患者有益。
