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.
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.
Authors: Benedikt Weber; Jérôme Robert; Agnieszka Ksiazek; Yves Wyss; Laura Frese; Jaroslav Slamecka; Debora Kehl; Peter Modregger; Silvia Peter; Marco Stampanoni; Steven Proulx; Volkmar Falk; Simon P Hoerstrup Journal: Tissue Eng Part C Methods Date: 2014-01-20 Impact factor: 3.056
Authors: Emanuela S Fioretta; Sarah E Motta; Valentina Lintas; Sandra Loerakker; Kevin K Parker; Frank P T Baaijens; Volkmar Falk; Simon P Hoerstrup; Maximilian Y Emmert Journal: Nat Rev Cardiol Date: 2020-09-09 Impact factor: 32.419
Authors: Maurizio Taramasso; Maximilian Y Emmert; Diana Reser; Andrea Guidotti; Nikola Cesarovic; Marino Campagnol; Alessandro Addis; Fabian Nietlispach; Simon P Hoerstrup; Francesco Maisano Journal: J Cardiovasc Transl Res Date: 2015-05-13 Impact factor: 4.132
Authors: Zeeshan Syedain; Jay Reimer; Jillian Schmidt; Matthew Lahti; James Berry; Richard Bianco; Robert T Tranquillo Journal: Biomaterials Date: 2015-09-11 Impact factor: 12.479
Authors: V Lintas; E S Fioretta; S E Motta; P E Dijkman; M Pensalfini; E Mazza; E Caliskan; H Rodriguez; M Lipiski; M Sauer; N Cesarovic; S P Hoerstrup; M Y Emmert Journal: J Cardiovasc Transl Res Date: 2018-08-13 Impact factor: 4.132