A novel translational model for fetoscopic intratracheal delivery of nanoparticles in piglets

Carlon, Marianne; Engels, Alexander; Bosch, Barbara; Joyeux, Luc; Cunha, Marina Gabriela Monteiro Carvalho Mori da; Vidovic, Dragana; Debyser, Zeger; Boeck, K. De; Neyrinck, Arne; Deprest, Jan

doi:10.1002/pd.4915

Cited by 6 publications

(4 citation statements)

References 39 publications

(90 reference statements)

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“…The trachea was inspected grossly for the presence of balloon deformation, and transverse tracheal sections were processed as described previously (Appendix S1) 15 . On fixed specimens, the tracheal circumference was measured, and histological tracheal changes were scored by an experienced pathologist blinded to the treatment groups, using a hierarchical scoring system of all anatomical elements (Appendix S1, Table S1, Figure S3) 15,16 .…”

Section: In-vivo Studymentioning

confidence: 99%

New device permitting non‐invasive reversal of fetal endoscopic tracheal occlusion: ex‐vivo and in‐vivo study

Basurto

Sananès

Verbeken

et al. 2020

Ultrasound in Obstet & Gyne

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The novel 'Smart-TO' balloon for fetal endoscopic tracheal occlusion (FETO) deflates both ex vivo and in vivo when exposed to the peripheral magnetic field around a magnetic resonance scanner. Occlusiveness and tracheal effects are similar to those of the clinical standard Goldbal2 system. What are the clinical implications of this work? This study provides proof of efficacy and safety of the Smart-TO balloon, both in a simulated in-utero environment and in the fetal lamb model. It is part of a series of experiments required before clinical implementation. Introduction of this device should reduce the burden for patients undergoing FETO.

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Section: In-vivo Studymentioning

confidence: 99%

New device permitting non‐invasive reversal of fetal endoscopic tracheal occlusion: ex‐vivo and in‐vivo study

Basurto

Sananès

Verbeken

et al. 2020

Ultrasound in Obstet & Gyne

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“…Fetal vector delivery furthermore allows efficient and homogenous distribution of injected particles which is likely promoted by their fluid filled nature. This was for example demonstrated in WT pigs and mice after fetal intratracheal delivery of fluospheres or rAAV2/6.2 47,107,108. Finally, tolerance to transgenes after fetal or neonatal transduction has been demonstrated for human FIX in mice and dogs.…”

mentioning

confidence: 91%

Roadmap for an early gene therapy for cystic fibrosis airway disease

2017

Self Cite

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Gene therapy provides a mutation-independent approach to treat or even cure CF airway disease. To develop a clinical candidate for CF gene therapy, a thorough examination of preclinical efficacy in relevant cell and animal models is a prerequisite. For a long time, the CF field was struggling with a lack of appropriate animal models for CF airway pathology. Since 2008, many different and complementary animal models have been generated that develop hallmarks of CF airway disease, including the CF pig, ferret, and rat. With this, a new era has arisen that allows investigating the efficacy of gene therapy beyond molecular and electrophysiological end-points. Successful gene therapy most likely requires an appropriate time window. CF lung pathology progresses with age and therefore an early treatment would be beneficial to prevent irreversible damage. In that regard, newborn screening programs and prenatal diagnosis already provide a basis to facilitate future preventive gene-based treatment. If successful, gene therapy for CF airway disease would markedly reduce the treatment burden and improve life quality and life expectancy of CF patients.

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“…Pulmonary tropism could be enhanced by modifying the carrier to bind to cell membranes of organ-specific cells 53 . Finally, local lung toxicity remains unclear in vivo , however it seems not to be significant in higher species 54 . This should not be underestimated because nanoparticles are taken up by local immune cells which may play critical roles in the induction and regulation of pulmonary immunity or inflammation 47 .…”

Section: Discussionmentioning

confidence: 99%

Prenatal VEGF Nano-Delivery Reverses Congenital Diaphragmatic Hernia-Associated Pulmonary Abnormalities

Loukogeorgakis,

Michielin,

Al-Juffali

et al. 2024

Preprint

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RationaleCongenital diaphragmatic hernia (CDH) results in lung hypoplasia. In severe cases, tracheal occlusion (TO) can be offered to promote lung growth. However the benefit is limited, and novel treatments are required to supplement TO. Vascular endothelial growth factor (VEGF) is downregulated in animal models of CDH and could be a therapeutic target, but its role in human CDH is not known.ObjectivesTo investigate whether VEGF supplementation could be a suitable treatment for CDH-associated lung pathology.MethodsFetal lungs from CDH patients were used to determine pulmonary morphology and VEGF expression. A novel humanex vivomodel of fetal lung compression recapitulating CDH features was developed and used to determine the effect of exogenous VEGF supplementation (Figure 1A). A nanoparticle-based approach for intra-pulmonary delivery of VEGF was developed by conjugating it on functionalized nanodiamonds (ND-VEGF) and was tested in experimental CDHin vivo.Measurements and Main ResultsVEGF expression was downregulated in distal pulmonary epithelium of human CDH fetuses in conjunction with attenuated cell proliferation. The compression model resulted in impaired branching morphogenesis similar to CDH and downregulation of VEGF expression in conjunction with reduced proliferation of terminal bud epithelial progenitors; these could be reversed by exogenous supplementation of VEGF. Prenatal delivery of VEGF with the ND-VEGF platform in CDH fetal rats resulted in lung growth and pulmonary arterial remodelling that was complementary to that achieved by TO alone with appearances comparable to healthy controls.ConclusionsThis innovative approach could have a significant impact on the treatment of CDH.

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A novel translational model for fetoscopic intratracheal delivery of nanoparticles in piglets

Cited by 6 publications

References 39 publications

New device permitting non‐invasive reversal of fetal endoscopic tracheal occlusion: ex‐vivo and in‐vivo study

New device permitting non‐invasive reversal of fetal endoscopic tracheal occlusion: ex‐vivo and in‐vivo study

Roadmap for an early gene therapy for cystic fibrosis airway disease

Prenatal VEGF Nano-Delivery Reverses Congenital Diaphragmatic Hernia-Associated Pulmonary Abnormalities

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