Minimally-invasive implantation of living tissue engineered heart valves: a comprehensive approach from autologous vascular cells to stem cells.
OBJECTIVE
The aim of this study was to demonstrate the feasibility of combining the novel heart valve replacement technologies of: 1) tissue engineering; and 2) minimally-invasive implantation based on autologous cells and composite self-expandable biodegradable biomaterials.


BACKGROUND
Minimally-invasive valve replacement procedures are rapidly evolving as alternative treatment option for patients with valvular heart disease. However, currently used valve substitutes are bioprosthetic and as such have limited durability. To overcome this limitation, tissue engineering technologies provide living autologous valve replacements with regeneration and growth potential.


METHODS
Trileaflet heart valves fabricated from biodegradable synthetic scaffolds, integrated in self-expanding stents and seeded with autologous vascular or stem cells (bone marrow and peripheral blood), were generated in vitro using dynamic bioreactors. Subsequently, the tissue engineered heart valves (TEHV) were minimally-invasively implanted as pulmonary valve replacements in sheep. In vivo functionality was assessed by echocardiography and angiography up to 8 weeks. The tissue composition of explanted TEHV and corresponding control valves was analyzed.


RESULTS
The transapical implantations were successful in all animals. The TEHV demonstrated in vivo functionality with mobile but thickened leaflets. Histology revealed layered neotissues with endothelialized surfaces. Quantitative extracellular matrix analysis at 8 weeks showed higher values for deoxyribonucleic acid, collagen, and glycosaminoglycans compared to native valves. Mechanical profiles demonstrated sufficient tissue strength, but less pliability independent of the cell source.


CONCLUSIONS
This study demonstrates the principal feasibility of merging tissue engineering and minimally-invasive valve replacement technologies. Using adult stem cells is successful, enabling minimally-invasive cell harvest. Thus, this new technology may enable a valid alternative to current bioprosthetic devices.
Schmidt
Dörthe
D
Clinic for Cardiovascular Surgery, University Hospital Zurich, Raemistrasse 100, Zurich, Switzerland.
Dijkman
Petra E
PE
Driessen-Mol
Anita
A
Stenger
Rene
R
Mariani
Christine
C
Puolakka
Arja
A
Rissanen
Marja
M
Deichmann
Thorsten
T
Odermatt
Bernhard
B
Weber
Benedikt
B
Emmert
Maximilian Y
MY
Zund
Gregor
G
Baaijens
Frank P T
FP
Hoerstrup
Simon P
SP
D000818:Animals; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology / Q000637:transplantation*; D005500:Follow-Up Studies; D006350:Heart Valve Prosthesis; D006351:Heart Valves; D019060:Minimally Invasive Surgical Procedures / Q000379:methods*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000637:transplantation*; D012756:Sheep; D033581:Stem Cell Transplantation / Q000379:methods*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014182:Transplantation, Autologous