期刊
EUROPEAN HEART JOURNAL
卷 32, 期 22, 页码 2830-2840出版社
OXFORD UNIV PRESS
DOI: 10.1093/eurheartj/ehr059
关键词
Minimally invasive; Heart valve; Tissue engineering; Bone marrow; Stem cells; Primate model
资金
- State Secretariat for Education and Research, Swiss Government [EX25-2010]
- State Secretariat for Education and Research, South African Government [EX25-2010]
- Research Infrastructure Support Programme [UID 65720]
- National Research Foundation
- Department of Science and Technology South Africa
- University Research Committee - University of Cape Town
- Claude Leon Foundation
- Swiss National Science Foundation [32-122273]
- European Commission [242008]
Aims A living heart valve with regeneration capacity based on autologous cells and minimally invasive implantation technology would represent a substantial improvement upon contemporary heart valve prostheses. This study investigates the feasibility of injectable, marrow stromal cell-based, autologous, living tissue engineered heart valves (TEHV) generated and implanted in a one-step intervention in non-human primates. Methods and results Trileaflet heart valves were fabricated from non-woven biodegradable synthetic composite scaffolds and integrated into self-expanding nitinol stents. During the same intervention autologous bone marrow-derived mononuclear cells were harvested, seeded onto the scaffold matrix, and implanted transapically as pulmonary valve replacements into non-human primates (n = 6). The transapical implantations were successful in all animals and the overall procedure time from cell harvest to TEHV implantation was 118 +/- 17 min. In vivo functionality assessed by echocardiography revealed preserved valvular structures and adequate functionality up to 4 weeks post implantation. Substantial cellular remodelling and in-growth into the scaffold materials resulted in layered, endothelialized tissues as visualized by histology and immunohistochemistry. Biomechanical analysis showed non-linear stress-strain curves of the leaflets, indicating replacement of the initial biodegradable matrix by living tissue. Conclusion Here, we provide a novel concept demonstrating that heart valve tissue engineering based on a minimally invasive technique for both cell harvest and valve delivery as a one-step intervention is feasible in non-human primates. This innovative approach may overcome the limitations of contemporary surgical and interventional bioprosthetic heart valve prostheses.
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