Regenerative medicine solutions in congenital diaphragmatic hernia

https://doi.org/10.1053/j.sempedsurg.2017.04.009Get rights and content

Abstract

Congenital diaphragmatic hernia (CDH) remains a major challenge and associated mortality is still significant. Patients have benefited from current therapeutic options, but most severe cases are still associated to poor outcome. Regenerative medicine is emerging as a valid option in many diseases and clinical trials are currently happening for various conditions in children and adults. We report here the advancement in the field which will help both in the understanding of further CDH development and in offering new treatment options for the difficult situations such as repair of large diaphragmatic defects and lung hypoplasia. The authors believe that advancements in regenerative medicine may lead to increase of CDH patients׳ survival.

Introduction

In the EU-27, approximately 2100 babies with congenital diaphragmatic hernia (CDH) are born annually. Mortality is still up to 30% due to insufficient lung growth and persistent pulmonary hypertension. In the Western world, >60% of cases are diagnosed at the latest by the second trimester screening ultrasound (US). In isolated cases, one can make an individualized prognosis and counsel parents about prenatal options. The ability to identify a future non-survivor prenatally warrants the search for a prenatal intervention that can avoid that outcome. Today, lung development can already be stimulated prenatally by fetal endoscopic tracheal occlusion (FETO). FETO prevents egress of lung liquid, causing increased pulmonary stretch, which accelerates lung growth.1 This has been clinically translated into a percutaneous procedure under local anesthesia, without serious maternal morbidity. FETO is associated with an apparent increase in survival from <15% to 50% (for left-sided cases) and reduction of early neonatal respiratory morbidity compared to historical controls.2, 3 This potential benefit is now being investigated in an ongoing global randomized clinical trial (RCT).4 Unfortunately, FETO is invasive and has an up to 25% risk for preterm delivery, partly offsetting the beneficial effects. Also, the maximum post-FETO survival reported is 50–60%, which in part is caused by insufficient airway growth and/or limited vascular development. Therefore, alternative strategies are required.5, 6

Section snippets

Regenerative solutions

Regenerative medicine combines tissue engineering and cell transplantation, with an aim of replacing damaged tissues and organs, using living cells.7 While degenerative diseases have represented the main focus of the field, new interesting approaches could have a major influence in the outcome of children affected by congenital malformations such as CDH. In particular, there are at least 3 levels on which translational research in this field could have a direct impact: (1) understanding the

Conclusion

In the era of prenatal diagnosis of CDH, patients should receive individualized counseling on expected outcome. In severe cases, prenatal interventions may be considered to reverse the expected poor outcome. The only currently available clinical option is surgery by fetoscopic endoluminal tracheal occlusion. This is an investigational procedure currently investigated in a global randomized clinical trial. FETO may however not lead to sufficient lung growth and/or cause prematurity. Therefore

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    • Cited by (0)

    P.D.C. is a NIHR Professor and he is supported by the Catapult Cell Therapy, the GOSHCC and GOSH NIHR Biomedical Research Centre׳s funding scheme. J.D.P. is a Clinical Researcher of the Flanders Research Foundation (FWO Vlaanderen; 1.8.012.07). This publication reflects the views only of the author, and the Commission cannot be held responsible for any use that may be made of the information contained therein.

    Our research is in part supported by an Innovative Engineering for Health award by the Wellcome Trust, United Kingdom (WT101957), the Engineering and Physical Sciences Research Council (EPSRC), United Kingdom (NS/A000027/1) and the Fetal Health Foundation (USA).

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