Author + information
- Received December 7, 2011
- Revision received March 13, 2012
- Accepted April 12, 2012
- Published online August 1, 2012.
- Maximilian Y. Emmert, MD⁎,†,‡,
- Benedikt Weber, MD⁎,†,
- Petra Wolint⁎,†,
- Luc Behr, VDM, PhD¶,
- Sebastien Sammut, PhD⁎,¶,
- Thomas Frauenfelder, MD§,
- Laura Frese, PhD⁎,†,
- Jacques Scherman, MD‡,
- Chad E. Brokopp, PhD⁎,†,
- Christian Templin, MD∥,
- Jürg Grünenfelder, MD†,‡,
- Gregor Zünd, MD⁎,†,‡,
- Volkmar Falk, MD‡ and
- Simon P. Hoerstrup, MD, PhD⁎,†,‡,⁎ ()
- ↵⁎Reprint requests and correspondence
: Dr. Simon P. Hoerstrup, Swiss Center for Regenerative Medicine and Clinic for Cardiovascular Surgery, University and University Hospital, Raemistrasse 100 Zurich, 8091 CH-Zürich, Switzerland
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.
- aortic valve
- stem cells
- tissue engineered heart valves
- transcatheter aortic valve implantation
Dr. Emmert was supported by the SPUM (Special Program University Medicine; Swiss National Science Foundation), and Dr. Weber was supported by the 7th Framework Programme, Life Valve, European Commission. Drs. Behr and Sammut are employees of IMM Recherche, Paris, France. Dr. Falk is a consultant for Valtech; and has received speaker fees from Medtronic and Edwards. Dr. Hoerstrup is scientific adviser of the Xeltis AG/Switzerland. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Emmert and Weber contributed equally to this paper.
- Received December 7, 2011.
- Revision received March 13, 2012.
- Accepted April 12, 2012.
- American College of Cardiology Foundation