Tissue-engineered bioprosthetic venous valve: A long-term study in sheep

Teebken, Omke E.; Puschmann, Carmen; Aper, Thomas; Haverich, Axel; Mertsching, Heike

doi:10.1053/ejvs.2002.1873

Cited by 51 publications

(56 citation statements)

References 15 publications

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“…9 In particular in the field of heart valve regeneration, several recent preclinical large animal trials involving sheep 14,15,17 and non-human primate models 16 showed promising initial results and underline the potential of this technology for future therapeutic concepts. Given the major complications when using xeno-or homogenic venous valve transplants, Teebken et al 37 investigated for the first time TEVVs based on a homologous decellularized matrix in the ovine model. After removal of cellular elements, the valves were repopulated with autologous myofibroblasts and implanted into the external jugular veins with patency up to 12 weeks.…”

Section: Discussionmentioning

confidence: 99%

Living-Engineered Valves for Transcatheter Venous Valve Repair

Weber

Robert

Książek

et al. 2014

Tissue Engineering Part C: Methods

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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 polyglycolic acid-poly-4-hydroxybutyrate composite scaffolds, integrated into self-expandable nitinol stents, were engineered from autologous ovine bonemarrow-derived mesenchymal stem cells (BM-MSCs) and endothelialized. After in vitro conditioning in a (flow) pulse duplicator system, the TEVVs 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 (GI), 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 scanning electron microscopy analysis, GI, 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 BM-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 CVI in the future.

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Section: Discussionmentioning

confidence: 99%

Living-Engineered Valves for Transcatheter Venous Valve Repair

Weber

Robert

Książek

et al. 2014

Tissue Engineering Part C: Methods

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“…Previously described general animal care guidelines were followed (12). One or two sheep were studied per day.…”

Section: Discussionmentioning

confidence: 99%

Balloon occlusion of the right main bronchus in an ovine model provides sufficient time for emergent interventions in massive pulmonary embolism

Fan

Liu²,

Öklü

et al. 2011

Diagn Interv Radiol

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“…Conduit patency requires the following: the conduit must have antithrombotic properties [13]; intima hypertrophy must not progress in anastomoses between the MPA and the conduit [29], the intima should be covered with neo-endothelial cells [30] and the flexibility and histological form of the valve in the conduit should be maintained [27]. Although Denacol exerts an antithrombotic effect [19], intima hypertrophy in anastomoses has been demonstrated in humans due to delayed healing of the vessel after positioning a small-caliber artificial vascular graft treated with antithrombotics [22].…”

Section: Discussionmentioning

confidence: 99%

Histological Study of Right Ventricle-Pulmonary Artery Valved Conduit Implantation (RPVC) in Dogs with Pulmonic Stenosis

Saida

Tanaka

Fukushima

et al. 2009

The Journal of Veterinary Medical Science

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ABSTRACT. We examined whether right ventricle-pulmonary artery valved conduit (RPVC) implantation can overcome the disadvantages of current procedures for pulmonic stenosis (PS). We histologically evaluated the feasibility of RPVC using a homograft in PS model dogs. Eight dogs underwent pulmonary artery banding (PAB) and then 12 weeks later were assigned to PAB (n=4) or PAB+RPVC (n=4) groups. Dogs in the PAB group received no treatment throughout the experimental period, whereas the PAB+RPVC group underwent RPVC. At 1 year after PAB, hearts and conduits were explanted from euthanized dogs and histologically evaluated. The ratios (%) of myocardial fibrosis on right ventricle (RV) epicardial, median and endocardial layers were significantly lower in the PAB+RPVC, than in the PAB group. The ratio of myocardial fibrosis on left ventricular (LV) epicardial and endocardial layers were significantly lower in the PAB+RPVC, than in the PAB group. Neo-intimal thickness in the anastomosis areas of the Denacol and PAB+RPVC groups was 42.77  30.19 and 88.30  27.24 m, respectively, with no significant differences between the groups. Calcification and neo-intima hypertrophy were not obvious in the valve area. Immunohistological staining showed that the internal surface of the anastomosis and intermediate areas were positive for endothelial cells. We concluded that RPVC using a bioprosthetic graft can apparently overcome the disadvantages of current procedures for pulmonic stenosis. KEY WORDS: endotherialization, myocardial fibrosis, pulmonary artery banding, pulmonic stenosis, valved conduit.J. Vet. Med. Sci. 71(4): 409-415, 2009 Pulmonic stenosis (PS) is a relatively frequent congenital narrowing of the right ventricular outflow tract that occurs in about 0.1% of all dogs [9]. Strategies for treating severe pulmonic stenosis include transventricular pulmonic dilation [8], closed patch-graft [3,24], open patch-graft [12] and balloon dilation [4,6,14,15] valvuloplasty. Patch-graft valvuloplasty is an effective radical treatment for PS, but it requires a cardiopulmonary bypass to stabilize the circulation, which cannot be performed at many institutions [21]. On the other hand, although balloon dilation valvuloplasty is a popular strategy, the results are inferior in dogs with PS accompanied by dysplasia of the pulmonic annulus and main pulmonary artery to those in dogs with PS alone [6]. Thus, we considered right ventricle (RV)-pulmonary artery valved conduit (RPVC) implantation to overcome the disadvantages of the current procedures. Implantation with the RPVC decreases right ventricular systolic pressure by forming a bypass and the procedure is less invasive because it can be performed under the beating heart. A bioprosthetic valved conduit has been used for RVOT reconstruction in humans [2]. Denacol-treated bioprosthetic implanted conduits are better assimilated and organized with the blood vasculature [19]; they are also thrombo-resistant and do not provoke the immune response [13]. Furthermore, the valve in the condu...

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Tissue-engineered bioprosthetic venous valve: A long-term study in sheep

Abstract: acellularisation and consecutive in vitro autogeneic re-seeding of valved venous conduits can lead to immunologically acceptable, patent, and competent implants in sheep.

Cited by 51 publications

References 15 publications

Living-Engineered Valves for Transcatheter Venous Valve Repair

Living-Engineered Valves for Transcatheter Venous Valve Repair

Balloon occlusion of the right main bronchus in an ovine model provides sufficient time for emergent interventions in massive pulmonary embolism

Histological Study of Right Ventricle-Pulmonary Artery Valved Conduit Implantation (RPVC) in Dogs with Pulmonic Stenosis

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