Experimental Models for Novel Therapies in Neonatal Surgery: Translational Approaches
18 September 2019 (online)
This review block section of the European Journal of Pediatric Surgery is dedicated to experimental models of neonatal surgical conditions and particularly focuses on the novel therapies that have emerged from their use and that are being translated into clinical practice.
Bruns et al have reviewed the available experimental treatment options for long-gap esophageal atresia and highlighted novel techniques. Numerous animal models, including the pig, rabbit, and rat, have been used to study the esophagus and to test novel techniques for this challenging form of esophageal atresia. The authors have analyzed in detail, all operative and nonoperative techniques, for long-gap esophageal atresia which include esophageal lengthening techniques for delayed anastomosis, for example, the botulinum toxin A injection, combined lengthening and anastomotic techniques, for example, magnetic compression anastomosis, and esophageal replacement which includes bioengineered scaffolds.
Antounians et al have reviewed the different models of congenital diaphragmatic hernia based on the use of chemicals, dietary changes, genetic alterations, and surgical maneuvers and have described how discoveries using these models have been translated to treat humans. In the first part, the authors have synthesized the literature on the use of teratogenic and genetic models in small rodents, such as the rat and the mouse, that have been important to further our knowledge on the pathophysiology of this multifactorial condition and on associated pulmonary hypoplasia and vascular remodeling. In the second part of this review, Antounians et al have examined the surgical models of diaphragmatic hernia that have been established in larger animals, such as the lamb and the rabbit, and have been useful for testing antenatal and postnatal therapies.
Biliary atresia is a challenging condition with an unknown etiology and poor clinical outcome. In their review, Madadi-Sanjani and Petersen have discussed the main experimental studies that are related to this condition which include a description of biliary atresia-like conditions in the wildlife, as well as the analysis of pre- and postnatal models of biliary atresia in animals, including virus-induced cholestasis in mice. This review also addresses the future of experimental studies on biliary atresia and what would be required for the progress of this condition.
Sbragia et al have reviewed the animal models of gastroschisis which have been in use for more than 35 years and have been instrumental for the understanding of the pathophysiology of the disease and for the testing of antenatal maneuvers. These experimental studies have reproduced gastroschisis in different animals and with different approaches, including transgenic mice and surgically created models in the rat, rabbit, lamb, and chick. These studies have helped us elucidate phenomena that cause gastroschisis morbidities, such as intestinal inflammation and dysmotility, and to investigate the efficacy of interventions to prevent them, such as the amniotic fluid exchange. In recent years, advancements in regenerative medicine have led to the testing of novel strategies, such as the transamniotic stem-cell therapy for bowel regeneration and the tissue engineering to repair abdominal wall defects.
Necrotizing enterocolitis remains one of the biggest challenges of neonatal surgery, with severe long-term morbidities affecting survivors and a mortality rate that has not changed over decades. Ganji et al have thoroughly examined the various models of the disease that range from the in vitro evaluation of intestinal epithelial cells and intestinal organoids to in vivo models of necrotizing enterocolitis in neonatal mice, rats, and piglets. In this review, the authors have discussed how these experimental studies have advanced our knowledge on the pathogenesis of this disease and how they have allowed us to investigate the effectiveness of novel therapeutic agents.
Fujiwara et al have reviewed the various animal models of Hirschsprung's disease that have further the understanding of the anatomy and pathophysiology of the disease and the discovery of gene mutations responsible for the development of Hirschsprung's disease. The authors have described the main four types of animal models that are teratogen-induced, surgically created, naturally occurring, and knockout models, and have summarized recent advances in this research field, highlighting the opportunities for new discoveries.
Lastly, Martins et al have reviewed the main experimental models of anorectal malformations in rodents (rabbit, rat, and mouse) and in the pig. The authors describe how some models occur naturally and how some can be induced by the administration of drugs, such as etretinate, ethylene thiourea, and Adriamycin. These experimental studies have elucidated the altered embryological processes that lead to the development of anorectal malformations and more recently have allowed the identification of the molecular mechanisms of this process, providing the basis for the application of tissue engineering in future experiments.
We are sure that this review block section of the European Journal of Pediatric Surgery will provide a thorough review of the existing literature on experimental neonatal surgery, will inform you on the advancements that have occurred in the specific research fields, and, most importantly, will update you on the cutting-edge research that is increasingly pervading our specialty. We have focused on research translational aspects, to ensure the reader becomes familiar with the new perspectives that are emerging in the laboratory and advances that might be implemented into future clinical practice.
- 1 Bruns NE, Glenn IC, Ponsky TA. Esophageal atresia: state of the art in translating experimental research to the bedside. Eur J Pediatr Surg 2019; 29 (04) 328-335
- 2 Antounians L, Figueira RL, Sbragia L, Zani A. Congenital diaphragmatic hernia: state of the art in translating experimental research to the bedside. Eur J Pediatr Surg 2019; 29 (04) 317-327
- 3 Madadi-Sanjani O, Petersen C. Translational research in biliary atresia: news from mice and men. Eur J Pediatr Surg 2019; 29 (04) 336-341
- 4 Sbragia L, Figueira RL, da Costa KM, Volpe FP. Gastroschisis: state of the art in translating experimental research to the bedside. Eur J Pediatr Surg 2019; 29 (04) 342-351
- 5 Ganji N, Li B, Lee C, Filler R, Pierro A. Necrotizing enterocolitis: state of the art in translating experimental research to the bedside. Eur J Pediatr Surg 2019; 29 (04) 352-360
- 6 Fujiwara N, Nakazawa-Tanaka N, Yamataka A. Animal models of hirschsprung's disease: state of the art in translating experimental research to the bedside. Eur J Pediatr Surg 2019; 29 (04) 361-367
- 7 Martins JL, Macedo M, de Souza Montero EF. Anorectal malformation: state of the art in translating experimental research to the bedside. Eur J Pediatr Surg 2019; 29 (04) 368-370