OBJECTIVES: Decellularized pulmonary homografts (DPH) have shown excellent results for pulmonary valve replacement. However, controlled multicentre studies are lacking to date.METHODS: Prospective... Show moreOBJECTIVES: Decellularized pulmonary homografts (DPH) have shown excellent results for pulmonary valve replacement. However, controlled multicentre studies are lacking to date.METHODS: Prospective European multicentre trial evaluating DPH for pulmonary valve replacement. Matched comparison of DPH to bovine jugular vein (BJV) conduits and cryopreserved homografts (CH) considering patient age, type of heart defect and previous procedures.RESULTS: In total, 121 patients (59 female) were prospectively enrolled (August 2014-December 2016), age 21.3 +/- 14.4 years, DPH diameter 24.4 +/- 2.8 mm. No adverse events occurred with respect to surgical handling; there were 2 early deaths (30 + 59 years) due to myocardial failure after multi-valve procedures and no late mortality (1.7% mortality). After a mean follow-up of 2.2 +/- 0.6 years, the primary efficacy end points mean peak gradient (16.1 +/- 12.1 mmHg) and regurgitation (mean 0.25 +/- 0.48, grade 0-3) were excellent. One reoperation was required for recurrent subvalvular stenosis caused by a pericardial patch and 1 balloon dilatation was performed on a previously stented LPA. 100% follow-up for DPH patients operated before or outside the trial (n = 114) included in the ESPOIR Registry, age 16.6 +/- 10.4 years, diameter 24.1 +/- 4.2 mm, follow-up 5.1 +/- 3.0 years. The combined DPH cohort, n = 235, comprising both Trial and Registry data showed significantly better freedom from explantation (DPH 96.7 +/- 2.1%, CH 84.4 +/- 3.2%, P = 0.029 and BJV 82.7 +/- 3.2%, P = 0.012) and less structural valve degeneration at 10 years when matched to CH, n = 235 and BJV, n = 235 (DPH 61.4 +/- 6.6%, CH 39.9 +/- 4.4%, n.s., BJV 47.5 +/- 4.5%, P = 0.029).CONCLUSIONS: Initial results of the prospective multicentre ESPOIR Trial showed DPH to be safe and efficient. Current DPH results including Registry data were superior to BJV and CH. Show less
Man, S.; Duffhues, G.S.; Dijke, P. ten; Baker, D. 2019
Pathologies of the respiratory system such as lung infections, chronic inflammatory lung diseases, and lung cancer are among the leading causes of morbidity and mortality, killing one in six people... Show morePathologies of the respiratory system such as lung infections, chronic inflammatory lung diseases, and lung cancer are among the leading causes of morbidity and mortality, killing one in six people worldwide. Development of more effective treatments is hindered by the lack of preclinical models of the human lung that can capture the disease complexity, highly heterogeneous disease phenotypes, and pharmacokinetics and pharmacodynamics observed in patients. The merger of two novel technologies, Organs-on-Chips and human stem cell engineering, has the potential to deliver such urgently needed models. Organs-on-Chips, which are microengineered bioinspired tissue systems, recapitulate the mechanochemical environment and physiological functions of human organs while concurrent advances in generating and differentiating human stem cells promise a renewable supply of patient-specific cells for personalized and precision medicine. Here, we discuss the challenges of modeling human lung pathophysiology in vitro, evaluate past and current models including Organs-on-Chips, review the current status of lung tissue modeling using human pluripotent stem cells, explore in depth how stem cell based Lung-on-Chips may advance disease modeling and drug testing, and summarize practical consideration for the design of Lung-on-Chips for academic and industry applications. (C) 2018 Elsevier B.V. All rights reserved. Show less
Bomer, N.; Hollander, W. den; Suchiman, H.; Houtman, E.; Slieker, R.C.; Heijmans, B.T.; ... ; Meulenbelt, I. 2016
