Prenatally engineered autologous amniotic fluid stem cell-based heart valves in the fetal circulation

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• 作者：Benedikt Weber^a ; Maximilian Y. Emmert^a ; Luc Behr^b ; Roman Schoenauer^a ; Chad Brokopp^a ; Cord Drö ; gemü ; ller^c ; Peter Modregger^d ; ^e ; Marco Stampanoni^d ; ^f ; Divya Vats^g ; Markus Rudin^g ; Wilfried Bü ; rzle^h ; Marc Farine^h ; Edoardo Mazza^h ; ⁱ ; Thomas Frauenfelder^j ; Andrew C. Zannettino^k ; Gregor Zü ; nd^a ; Oliver Kretschmar^l ; Volkmar Falk^a ; Simon P. Hoerstrup^a ; ^{simon_philipp.hoerstrup@usz.ch}
• 关键词：Amniotic fluid stem cells ; Composite matrix ; Fetal model ; Heart valve ; Prenatal intervention ; Tissue engineering
• 刊名：Biomaterials
• 出版年：2012
• 期刊代码：7_01429612
• 类别：ms
• 出版时间：June, 2012
• 卷：33
• 期：16
• 页码：4031-4043
• 文件大小：5454 K

摘要

Prenatal heart valve interventions aiming at the early and systematic correction of congenital cardiac malformations represent a promising treatment option in maternal-fetal care. However, definite fetal valve replacements require growing implants adaptive to fetal and postnatal development. The presented study investigates the fetal implantation of prenatally engineered living autologous cell-based heart valves. Autologous amniotic fluid cells (AFCs) were isolated from pregnant sheep between 122 and 128 days of gestation via transuterine sonographic sampling. Stented trileaflet heart valves were fabricated from biodegradable PGA-P4HB composite matrices (n聽=聽9) and seeded with AFCs in聽vitro. Within the same intervention, tissue engineered heart valves (TEHVs) and unseeded controls were implanted orthotopically into the pulmonary position using an in-utero closed-heart hybrid approach. The transapical valve deployments were successful in all animals with acute survival of 77.8%of fetuses. TEHV in-vivo functionality was assessed using echocardiography as well as angiography. Fetuses were harvested up to 1 week after implantation representing a birth-relevant gestational age. TEHVs showed in聽vivo functionality with intact valvular integrity and absence of thrombus formation. The presented approach may serve as an experimental basis for future human prenatal cardiac interventions using fully biodegradable autologous cell-based living materials.