Early and late failure of tissue-engineered pulmonary valve conduits used for right ventricular outflow tract reconstruction in patients with congenital heart disease

Perri, Gianluigi; Polito, Angelo; Esposito, Claudia; Albanese, Sonia B.; Francalanci, Paola; Pongiglione, Giacomo; Carotti, Adriano

doi:10.1093/ejcts/ezr221

Cited by 75 publications

(55 citation statements)

References 22 publications

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“…52 A larger trial with decellularized porcine valves in 93 patients showed freedom from conduit failure to be 60% at 24 months and below 25% after 36 months. 53 In this study by Perri et al, there was no single cause of failure, but histology showed the presence of inflammatory giant cells in the explanted valves. While immune compatibility of decellularized native valves can potentially be resolved, another challenge with tissue valves in pediatric patients is the elevated risk of ECM degradation and calcification.…”

Section: Discussionmentioning

confidence: 56%

Decellularized Tissue-Engineered Heart Valve Leaflets with Recellularization Potential

Syedain

Bradee

Kren

et al. 2013

Tissue Engineering Part A

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Tissue-engineered heart valves (TEHV) have been proposed as a promising solution for the clinical needs of pediatric patients. In vivo studies have shown TEHV leaflet contraction and regurgitation after several months of implantation. This has been attributed to contractile cells utilized to produce the extracellular matrix (ECM) during TEHV culture. Here, we utilized such cells to develop a mature ECM in a fibrin-based scaffold that generates commissural alignment in TEHV leaflets and then removed these cells using detergents. Further, we evaluated recellularization with potentially noncontractile cells. A tissue-engineered leaflet model was developed with mechanical anisotropy and tensile properties comparable to an ovine pulmonary valve leaflet. No change in tensile properties occurred after decellularization using 1% sodium dodecyl sulfate and 1% Triton detergent treatment. Cell removal was verified by DNA quantitation and western blot analysis for cellular proteins. Histological and scanning electron microscope imaging showed no significant change in the ECM organization and microstructure. We further tested the recellularization potential of decellularized leaflets by seeding human mesenchymal stem cells (hMSC) on the surface of the leaflets and evaluated them at 1 and 3 weeks in two culture conditions. One medium (M1) was chosen to maintain the MSC phenotype while a second medium (M2) was used to potentially differentiate cells to an interstitial cell phenotype. Cellular quantitation showed that the engineered leaflets were recellularized to the highest concentration with M2 followed by M1, with minimum cell invasion of decellularized native leaflets. Histology showed cellular invasion throughout the thickness of the leaflets in M2 and partial invasion in M1. hMSC stained positive for MSC markers, but also for asmooth muscle actin in both media at 1 week, with no presence of MSC markers at 3 weeks with the exception of CD90. These results show that engineered leaflets, while having similar tensile properties and collagen content compared to native leaflets, have better recellularization potential.

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Section: Discussionmentioning

confidence: 56%

Decellularized Tissue-Engineered Heart Valve Leaflets with Recellularization Potential

Syedain

Bradee

Kren

et al. 2013

Tissue Engineering Part A

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“…[26][27][28] Later reports on the performance of these valves were, however, variable. [29][30][31] Cicha et al 32 reported on four adolescent patients implanted with Matrix P valves, who were reoperated due to early to midterm graft failure (12-15 months). The explanted valves showed massive inflammatory and fibrotic responses at the distal region, lumen narrowing, and low recolonization of the decellularized matrix.…”

Section: Introductionmentioning

confidence: 99%

Regenerative Potential of Low-Concentration SDS-Decellularized Porcine Aortic Valved Conduits In Vivo

Gutierrez

Berry

Korossis

et al. 2015

Tissue Engineering Part A

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The aims of this study were to determine the functional biocompatibility of low-concentration SDS-decellularized porcine aortic roots in vivo. A previously developed process was modified for 9- and 15-mm-diameter aortic roots to facilitate implantation into the porcine abdominal aorta (n=3) and juvenile sheep right ventricular outflow tract (n=7), respectively. Native allogeneic aortic roots were used as controls. Acellular porcine roots explanted from pigs at weeks were largely repopulated with stromal cells of appropriate phenotype, and there was evidence that macrophages were involved in the regenerative process. Native allogeneic roots were subject to a classic allograft rejection response. Acellular porcine roots explanted from sheep at 6 months showed evidence of appropriate cellular repopulation, again with evidence of a role for macrophages in the regenerative process. There was some degree of calcification of two of the explanted acellular roots, likely due to incomplete removal of DNA before implantation. Native allogeneic ovine roots were subject to a classic allograft rejection response involving T cells, which resulted in overtly calcified and damaged tissues. The study highlighted (1) the importance of removal of DNA from acellular porcine valved roots to avoid calcification and (2) a role for macrophages in the regeneration of low-concentration SDS-decellularized aortic roots, as has been reported for other acellular biological extracellular matrix scaffolds.

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“…SV, stroke volume. authors show promising results at 3 years follow-up, 2 others report high early conduit failure rate 1,3 making the pursuit for the ideal TEHV conduit especially for children and young adults paramount. Decellularized TEHVs based on biodegradable synthetic materials may serve as suitable replacement of allografts and xenografts, but preclinical study in nonhuman primate and ovine models are characterized by valvular regurgitation due to leaflet shortening and reduced leaflet coaptation.…”

Section: Discussionmentioning

confidence: 99%

“…Xenografts and human cryopreserved valves are characterized by increased early reintervention rates due to strong immunological reactions with subsequent calcification. [1][2][3] The lack of growth potential also predisposes children to recurrent surgeries thus increasing morbidity. Decellularized allograft heart valves have been used as tissue-engineered heart valve (TEHV) scaffolds by several investigators with promising results, 4,5 however, little is known about the cellular mechanisms underlying neotissue formation in these TEHVs.…”

mentioning

confidence: 99%

Hemodynamic Characterization of a Mouse Model for Investigating the Cellular and Molecular Mechanisms of Neotissue Formation in Tissue-Engineered Heart Valves

James

Tara

et al. 2015

Tissue Engineering Part C: Methods

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Decellularized allograft heart valves have been used as tissue-engineered heart valve (TEHV) scaffolds with promising results; however, little is known about the cellular mechanisms underlying TEHV neotissue formation. To better understand this phenomenon, we developed a murine model of decellularized pulmonary heart valve transplantation using a hemodynamically unloaded heart transplant model. Furthermore, because the hemodynamics of blood flow through a heart valve may influence morphology and subsequent function, we describe a modified loaded heterotopic heart transplant model that led to an increase in blood flow through the pulmonary valve. We report host cell infiltration and endothelialization of implanted decellularized pulmonary valves (dPV) and provide an experimental approach for the study of TEHVs using mouse models.

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Early and late failure of tissue-engineered pulmonary valve conduits used for right ventricular outflow tract reconstruction in patients with congenital heart disease

Abstract: Compared with the other conduit for RVOTR Matrix conduits showed a high incidence of failure. Our results suggest that the use of Matrix conduits for RVOTR should be considered with caution.

Cited by 75 publications

References 22 publications

Decellularized Tissue-Engineered Heart Valve Leaflets with Recellularization Potential

Decellularized Tissue-Engineered Heart Valve Leaflets with Recellularization Potential

Regenerative Potential of Low-Concentration SDS-Decellularized Porcine Aortic Valved Conduits In Vivo

Hemodynamic Characterization of a Mouse Model for Investigating the Cellular and Molecular Mechanisms of Neotissue Formation in Tissue-Engineered Heart Valves

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