Fioretta Emanuela S, Lintas Valentina, Mallone Anna, Motta Sarah E, von Boehmer Lisa, Dijkman Petra E, Cesarovic Nikola, Caliskan Etem, Rodriguez Cetina Biefer Héctor, Lipiski Miriam, Sauer Mareike, Putti Matilde, Janssen Henk M, Söntjens Serge H, Smits Anthal I P M, Bouten Carlijn V C, Emmert Maximilian Y, Hoerstrup Simon P
Institute for Regenerative Medicine, University of Zürich, Zürich, Switzerland.
Wyss Translational Center Zürich, University of Zürich and ETH Zürich, Zürich, Switzerland.
JACC Basic Transl Sci. 2019 Dec 11;5(1):15-31. doi: 10.1016/j.jacbts.2019.09.008. eCollection 2020 Jan.
This study showed that bone marrow mononuclear cell pre-seeding had detrimental effects on functionality and in situ remodeling of bioresorbable bisurea-modified polycarbonate (PC-BU)-based tissue-engineered heart valves (TEHVs) used as transcatheter pulmonary valve replacement in sheep. We also showed heterogeneous valve and leaflet remodeling, which affects PC-BU TEHV safety, challenging their potential for clinical translation. We suggest that bone marrow mononuclear cell pre-seeding should not be used in combination with PC-BU TEHVs. A better understanding of cell-scaffold interaction and in situ remodeling processes is needed to improve transcatheter valve design and polymer absorption rates for a safe and clinically relevant translation of this approach.
本研究表明,在绵羊经导管肺动脉瓣置换术中,预接种骨髓单个核细胞对基于生物可吸收双脲改性聚碳酸酯(PC-BU)的组织工程心脏瓣膜(TEHV)的功能和原位重塑具有不利影响。我们还展示了瓣膜和瓣叶的异质性重塑,这影响了PC-BU TEHV的安全性,对其临床转化潜力提出了挑战。我们建议,不应将预接种骨髓单个核细胞与PC-BU TEHV联合使用。需要更好地理解细胞-支架相互作用和原位重塑过程,以改进经导管瓣膜设计和聚合物吸收率,从而实现该方法安全且与临床相关的转化。