In vitro investigation of the differentiation of enteric neural crest-derived cells following transplantation of aganglionic gut in a mouse model
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Read the article on link.springer.com ↗Article · Mar 2022 · 1 min read
In brief
In brief
Mouse model study demonstrates that enteric neural crest-derived cells transplanted into aganglionic (Hirschsprung disease) gut show impaired migration and differentiation compared to normal gut tissue. Findings suggest the recipient gut microenvironment critically influences stem cell therapy outcomes for enteric neuropathies.
Written by the GCMD Library team from the article.
Abstract
Purpose
Cell therapy is a promising approach to treat enteric neuropathies such as Hirschsprung disease (HD). Recent studies have reported that enteric neurons derived from stem cells (ENCCs) can be grafted into the HD colon. Thus, we investigated the migration and generation of enteric neurospheres from SOX10-VENUS+ mice after transplantation into control or Ednrb KO mice, which are a model of HD.
Methods
Single-cell suspensions were isolated from the fetal guts of SOX10-VENUS+ mice E13.5 and dissociated. These cells were cultured for 7 days under non-adherent conditions to generate neurospheres, which were co-cultured with dissociated control or SOX10-VENUS− Ednrb KO mouse gut on E13.5. 4 days later, these cells were fixed and the expression of the neuronal marker, Tuj1, was evaluated.
Results
Transplanted neurospheres had undergone abundant neuronal migration and differentiation of ENCCs in the control gut compared with the HD gut. The average length and intersections were significantly decreased in HD colon compared with controls (p < 0.05), and a similar pattern was observed in the HD small intestine (p < 0.05).
Conclusions
We demonstrated that transplanted ENCCs did not differentiate properly in HD gut. These results highlight the importance of the neuronal environment in the recipient gut for enteric nervous system development.