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- Title
In vitro investigation of the differentiation of enteric neural crest-derived cells following transplantation of aganglionic gut in a mouse model.
- Authors
Fujiwara, Naho; Miyahara, Katsumi; Nakazawa-Tanaka, Nana; Akazawa, Chihiro; Yamataka, Atsuyuki
- 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.
- Subjects
CELL transplantation; ENTERIC nervous system; LABORATORY mice; ANIMAL disease models; HIRSCHSPRUNG'S disease
- Publication
Pediatric Surgery International, 2022, Vol 38, Issue 5, p755
- ISSN
0179-0358
- Publication type
Article
- DOI
10.1007/s00383-022-05105-2