Stem Cell-Based Transcatheter Aortic Valve Implantation First Experiences in a Pre-Clinical Model

被引：57

作者：

Emmert, Maximilian Y. ^{[1
,2
,3
,4
]}

Weber, Benedikt ^{[1
,2
,3
]}

Wolint, Petra ^{[1
,2
,3
]}

Behr, Luc ^{[7
]}

Sammut, Sebastien ^{[1
,2
,7
]}

Frauenfelder, Thomas ^{[5
]}

Frese, Laura ^{[1
,2
,3
]}

Scherman, Jacques ^{[4
]}

Brokopp, Chad E. ^{[1
,2
,3
]}

Templin, Christian ^{[6
]}

Gruenenfelder, Juerg ^{[3
,4
]}

Zuend, Gregor ^{[1
,2
,3
,4
]}

Falk, Volkmar ^{[4
]}

Hoerstrup, Simon P. ^{[1
,2
,3
,4
]}

机构：

[1] Univ Zurich, Swiss Ctr Regenerat Med, CH-8091 Zurich, Switzerland

[2] Univ Zurich Hosp, CH-8091 Zurich, Switzerland

[3] Univ Zurich Hosp, Dept Surg Res, CH-8091 Zurich, Switzerland

[4] Univ Zurich Hosp, Cardiovasc Surg Clin, CH-8091 Zurich, Switzerland

[5] Univ Zurich Hosp, Dept Radiol, CH-8091 Zurich, Switzerland

[6] Univ Zurich Hosp, Clin Cardiol, CH-8091 Zurich, Switzerland

[7] Inst Mutualiste Montsouris, IMM Rech, Paris, France

来源：

JACC-CARDIOVASCULAR INTERVENTIONS | 2012年 / 5卷 / 08期

基金：

欧盟第七框架计划; 瑞士国家科学基金会;

关键词：

aortic valve; stem cells; tissue engineered heart valves; transcatheter; transcatheter aortic valve implantation; ENGINEERED VASCULAR GRAFTS; HEART-VALVES; TISSUE; REPLACEMENT; STENOSIS;

D O I：

10.1016/j.jcin.2012.04.010

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Objectives This study sought to investigate the combination of transcatheter aortic valve implantation and a novel concept of stem cell-based, tissue-engineered heart valves (TEHV) comprising minimally invasive techniques for both cell harvest and valve delivery. Background TAVI represents an emerging technology for the treatment of aortic valve disease. The used bioprostheses are inherently prone to calcific degeneration and recent evidence suggests even accelerated degeneration resulting from structural damage due to the crimping procedures. An autologous, living heart valve prosthesis with regeneration and repair capacities would overcome such limitations. Methods Within a 1-step intervention, trileaflet TEHV, generated from biodegradable synthetic scaffolds, were integrated into self-expanding nitinol stents, seeded with autologous bone marrow mononuclear cells, crimped and transapically delivered into adult sheep (n = 12). Planned follow-up was 4 h (Group A, n = 4), 48 h (Group B, n = 5) or 1 and 2 weeks (Group C, n = 3). TEHV functionality was assessed by fluoroscopy, echocardiography, and computed tomography. Post-mortem analysis was performed using histology, extracellular matrix analysis, and electron microscopy. Results Transapical implantation of TEHV was successful in all animals (n = 12). Follow-up was complete in all animals of Group A, three-fifths of Group B, and two-thirds of Group C (1 week, n = 1; 2 weeks, n = 1). Fluoroscopy and echocardiography displayed TEHV functionality demonstrating adequate leaflet mobility and coaptation. TEHV showed intact leaflet structures with well-defined cusps without signs of thrombus formation or structural damage. Histology and extracellular matrix displayed a high cellularity indicative for an early cellular remodeling and in-growth after 2 weeks. Conclusions We demonstrate the principal feasibility of a transcatheter, stem cell-based TEHV implantation into the aortic valve position within a 1-step intervention. Its long-term functionality proven, a stem cell-based TEHV approach may represent a next-generation heart valve concept. (J Am Coll Cardiol Intv 2012; 5: 874-83) (C) 2012 by the American College of Cardiology Foundation

引用

页码：874 / 883

页数：10

共 27 条

[1]

Tissue-engineered vascular grafts demonstrate evidence of growth and development when implanted in a juvenile animal model [J].