Decellularized aortic allografts versus pulmonary autografts for aortic valve replacement in the growing sheep model: haemodynamic and morphological results at 20 months after implantation

Tudorache, I.; Theodoridis, Karolina; Baraki, Hassina; Sarikouch, Samir; Bara, Christoph; Meyer, Tanja; Höffler, Klaus; Hartung, Dagmar; Hilfiker, Andres; Haverich, Axel; Cebotari, Serghei

doi:10.1093/ejcts/ezv362

Cited by 37 publications

(45 citation statements)

References 21 publications

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“…In previous studies, the combination of these 2 detergents has been successfully used to convert pulmonary valve allografts in cell-free scaffolds. The grafts also proved to exhibit excellent biomechanical stability [Tudorache et al, 2007] and in vivo performance [Tudorache et al, 2007[Tudorache et al, , 2016Theodoridis et al, 2015]. No signs of adverse detergent-related effects on the extracellular matrix ultrastructure and its cytocompatibility properties were found when using lower detergent concentrations [Cebotari et al, 2010] similar to those used in the current study.…”

Section: Discussionmentioning

confidence: 56%

Tissue Engineering of Vein Valves Based on Decellularized Natural Matrices

Mogaldea

Goecke²,

Theodoridis³

et al. 2017

Cells Tissues Organs

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Valvular repair or transplantation, designed to restore the venous valve function of the legs, has been proposed as treatment in chronic venous insufficiency. Available grafts or surgeries have provided limited durability so far. Generating venous valve substitutes by means of tissue engineering could be a solution. We generated decellularized jugular ovine vein conduits containing valves (oVVC) after reseeding with ovine endothelial cells differentiated from peripheral blood-derived endothelial cells (oPBEC), cultivated in vitro corresponding to the circulatory situation in the lower leg at rest and under exertion. oVVC were decellularized by detergent treatment. GFP-labeled oPBEC were seeded onto the luminal side of the decellularized oVVC and cultivated under static-rotational conditions for 6 h (group I) and 12 h (group II), respectively. Reseeded matrices of group I were exposed to continuous low flow conditions (“leg at rest”). The tissues of group II were exposed to a gradually increasing flow (“leg under effort”). After 5 days, the grafts of group I revealed a uniform luminal endothelial cell coverage of the examined areas of the venous walls and adjacent venous valve leaflets. In group II, the cell coverage on luminal areas of the venous wall parts was found to be nearly complete. The endothelial cell coverage of adjacent venous valve leaflets was revealed to be less dense and confluent. Endothelial cells cultured on acellular vein tissues of both groups were distinctly orientated uniformly in the flow direction, clearly creating a stable and flow-orientated layer. Thus, an endothelium could successfully be reestablished on the luminal surface of a decellularized venous valve by seeding peripheral blood endothelial cells and culturing under different conditions.

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Section: Discussionmentioning

confidence: 56%

Tissue Engineering of Vein Valves Based on Decellularized Natural Matrices

Mogaldea

Goecke²,

Theodoridis³

et al. 2017

Cells Tissues Organs

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“…In a further attempt to overcome the residual immunological response, other research groups started clinical trialing, still ongoing, with pulmonary and aortic homografts decellularized with detergent-based procedures following preclinical animal model investigations [1, 4, 13]. At present, the longest experimental follow-up in an animal model was achieved with detergent-based preparations implanted in pig and sheep [14, 15]. Reported data confirmed the absence of valvular dysfunction or degeneration outcomes, while revealing a well-documented, though partly irregular, repopulation by the host cells.…”

Section: Introductionmentioning

confidence: 99%

Natural Scaffolds for Regenerative Medicine: Direct Determination of Detergents Entrapped in Decellularized Heart Valves

Dettin

Zamuner

Naso

et al. 2017

BioMed Research International

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The increasing urgency for replacement of pathological heart valves is a major stimulus for research on alternatives to glutaraldehyde-treated grafts. New xenogeneic acellular heart valve substitutes that can be repopulated by host cells are currently under investigation. Anionic surfactants, including bile acids, have been widely used to eliminate the resident cell components chiefly responsible for the immunogenicity of the tissue, even if detergent toxicity might present limitations to the survival and/or functional expression of the repopulating cells. To date, the determination of residual detergent has been carried out almost exclusively on the washings following cell removal procedures. Here, a novel HPLC-based procedure is proposed for the direct quantification of detergent (cholate, deoxycholate, and taurodeoxycholate) residues entrapped in the scaffold of decellularized porcine aortic and pulmonary valves. The method was demonstrated to be sensitive, reproducible, and extendable to different types of detergent. This assessment also revealed that cell-depleted heart valve scaffolds prepared according to procedures currently considered for clinical use might contain significant amount of surfactant.

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“…Recently, some researchers have investigated in vivo recellularization capacity by implanting nonrecellularized acellular scaffolds into animal models and humans [Honge et al, 2011;Assmann et al, 2013;Williams et al, 2015;Tudorache et al, 2016]. However, incomplete repopulation of the interstitium, even 2-6 months [Honge et al, 2011;Assmann et al, 2013;Williams et al, 2015] or 20 months [Tudorache et al, 2016] after implantation, remains a problem.…”

Section: Discussionmentioning

confidence: 99%

“…However, incomplete repopulation of the interstitium, even 2-6 months [Honge et al, 2011;Assmann et al, 2013;Williams et al, 2015] or 20 months [Tudorache et al, 2016] after implantation, remains a problem. The spontaneous in vivo reendothelialization in these studies has also often been shown to be incomplete [Baraki et al, 2009;Honge et al, 2011;Williams et al, 2015].…”

Section: Discussionmentioning

confidence: 99%

Complete Static Repopulation of Decellularized Porcine Tissues for Heart Valve Engineering: An in vitro Study

Roosens

Asadian²,

Somers³

et al. 2017

Cells Tissues Organs

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To date, a completely in vitro repopulated tissue-engineered heart valve has not been developed. This study focused on sequentially seeding 2 cell populations onto porcine decellularized heart valve leaflets (HVL) and pericardia (PER) to obtain fully repopulated tissues. For repopulation of the interstitium, porcine valvular interstitial cells (VIC) and bone marrow-derived mesenchymal stem cells (BM-MSC) or adipose tissue-derived stem cells (ADSC) were used. In parallel, the culture medium was supplemented with ascorbic acid 2-phosphate (AA) and its effect on recolonization was investigated. Subsequently and in order to obtain an endothelial surface layer similar to those in native HVL, valvular endothelial cells (VEC) were seeded onto the scaffolds. It was shown that VIC efficiently recolonized HVL and partially also PER. On the other hand, stem cells only demonstrated limited or no subsurface cell infiltration of HVL and PER. Interestingly, the addition of AA increased the migratory capacity of both stem cell populations. However, this was more pronounced for BM-MSC, and recolonization of HVL appeared to be more efficient than that of PER tissue. VEC were demonstrated to generate a new endothelial layer on HVL and PER. However, scanning microscopy revealed that these endothelial cells were not allowed to fully spread onto PER. This study provided a proof of concept for the future generation of a bioactive tissue-engineered heart valve by showing that bioactive HVL could be generated in vitro within 14 days via complete repopulation of the interstitium with BM-MSC or VIC and subsequent generation of an entirely new endothelium.

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Decellularized aortic allografts versus pulmonary autografts for aortic valve replacement in the growing sheep model: haemodynamic and morphological results at 20 months after implantation

Cited by 37 publications

References 21 publications

Tissue Engineering of Vein Valves Based on Decellularized Natural Matrices

Tissue Engineering of Vein Valves Based on Decellularized Natural Matrices

Natural Scaffolds for Regenerative Medicine: Direct Determination of Detergents Entrapped in Decellularized Heart Valves

Complete Static Repopulation of Decellularized Porcine Tissues for Heart Valve Engineering: An in vitro Study

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