Animal Models of Hirschsprung's Disease: State of the Art in Translating Experimental Research to the Bedside

Abstract

Hirschsprung's disease (HSCR) is caused by incomplete colonization of enteric neural crest-derived cell (ENCC) in the bowel, the failure of ENCCs to proliferate, differentiate, and migrate leads to an absence of enteric neurons in the distal colon, resulting in colonic motility dysfunction. Various animal models of HSCR have been important in the understanding of the anatomy and pathophysiology of the disease and in the discovery of genes involved in HSCR. Four types of HSCR animal models have been developed: teratogen-induced, surgically created, naturally occurring models, and knockout models. Mutations in several genes affect enteric nervous system (ENS) development and can have pleiotropic effects on this system. Furthermore, certain animal models are informative regarding how such molecules control the development and functional differentiation of the ENS. In this article, we summarize recent advances in this field and highlight opportunities for new discoveries.

Fecal microbiota transplantation enhances cell therapy in a rat model of hypoganglionosis by SCFA‐induced MEK1/2 signaling pathway

“…Thus, we used the BAC-induced model in this study. In addition, the permeability or activity range of BAC is limited to seromuscular layers, we assumed that the "hypoganglionic intestinal extract" and microbiota disorder could directly result from the lower number of enteric neurons/ganglia but not BAC treatment, which needs further study (Fujiwara et al, 2019;Soret et al, 2020). ◀ Figure 7.…”

An Update on the Insight of Embryonic, Etiopathogenesis, Current Surgical Advances Besides the Advocated ERNICA Guidelines for the Management of Rectosigmoid Hirschsprung Disease, and Clinical Referral Score Model for Early Diagnosis with Future Use of Stem Cells - A Systematic Review

“…Hence Stamp., et al [20], were forced to do a colostomy for the escalation of life span for studying them in the form of models for HSCR [20]. With the advent of methods like teratogens utilization, surgical methods apart from gene knock out for the induction of HSCR [21]. Now enough evidence exists that HSCR is a heritable disorder, with about 10-20% of subjects revealing a positive family history, whereas In rest it takes place just as a sporadic manifestation [22].…”

Stem cell-based therapy for hirschsprung disease, do we have the guts to treat?

“…According to the authors, the failure of engraftment in the remaining three mice is attributed to the technical difficulty of targeting the thin gut of the mouse model. The potential of endoscopic delivery could be further studied by testing on large animal models where endoscopic ultrasonography could be applied to examine layer-specific delivery [ 83 , 84 ].…”