Document Detail

Living engineered valves for transcatheter venous valve repair.
MedLine Citation:
PMID:  24156382     Owner:  NLM     Status:  Publisher    
Background: Chronic venous insufficiency (CVI) represents a major global health problem with increasing prevalence and morbidity. CVI is due to an incompetence of the venous valves, which causes venous reflux and distal venous hypertension. Several studies have focused on the replacement of diseased venous valves using xeno- and allogenic transplants, so far with moderate success due to immunologic and thromboembolic complications. Autologous cell-derived tissue engineered venous valves (TEVVs) based on fully biodegradable scaffolds could overcome these limitations by providing non-immunogenic, non-thrombogenic constructs with remodeling and growth potential. Methods: Tri- and bicuspid venous valves (n=27) based on PGA-P4HB composite scaffolds, integrated into self-expandable nitinol stents, were engineered from autologous ovine bone marrow-derived mesenchymal stem cells (MSCs) and endothelialized. After in vitro conditioning in a (flow) pulse duplicator system, the tissue engineered venous valves were crimped (n=18) and experimentally delivered (n=7). The effects of crimping on the tissue engineered constructs were investigated using histology, immunohistochemistry, scanning electron microscopy, grating interferometry and planar fluorescence reflectance imaging. Results: The generated TEVVs showed layered tissue formation with increasing collagen and glycosaminoglycan levels dependent on the duration of in vitro conditioning. After crimping no effects were found on the MSC-level in SEM analysis, grating interferometry, histology and extracellular matrix analysis. However, substantial endothelial cell loss was detected after the crimping procedure, which could be reduced by increasing the static conditioning phase. Conclusions: Autologous living small diameter TEVVs can be successfully fabricated from ovine bone marrow-derived MSCs using a (flow) pulse duplicator conditioning approach. These constructs hold the potential to overcome the limitations of currently used non-autologous replacement materials and may open new therapeutic concepts for the treatment of chronic venous insufficiency in the future.
Benedikt Weber; Jerome Robert; Agnieszka Ksiazek; Yves Wyss; Laura Frese; Jaroslav Slamecka; Debora Kehl; Peter Modregger; Sylvia Peter; Marco Stampanoni; Steven Proulx; Simon P Hoerstrup; Volkmar Falk
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-10-25
Journal Detail:
Title:  Tissue engineering. Part C, Methods     Volume:  -     ISSN:  1937-3392     ISO Abbreviation:  Tissue Eng Part C Methods     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2013-10-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101466663     Medline TA:  Tissue Eng Part C Methods     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Swiss Center of Regenerative Medicine, University and University Hospital of Zurich, Switzerland., Zurich, Switzerland ;
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