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Pediatric Surgery International

Erschienen in:

01.12.2023 | Original Article

The impact of the recipient intestinal site on the differentiation of transplanted enteric neural crest cells

verfasst von: Nana Nakazawa-Tanaka, Naho Fujiwara, Katsumi Miyahara, Chihiro Akazawa, Masahiko Urao, Atsuyuki Yamataka

Erschienen in: Pediatric Surgery International | Ausgabe 1/2023

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Abstract

Purpose

It has long been established that the failure of enteric neural crest cells (ENCCs) to colonize the entire gut results in aganglionosis at the distal colon in Hirschsprung disease (HD). However, it is still unclear how the intestinal microenvironment of the distal aganglionic gut differs from that of the proximal ganglionic gut in HD versus normal gut. We have recently succeeded in transplanting ENCC into aganglionic gut in endothelin receptor B (Ednrb) knockout (KO) mice. to advance the development of cell therapy for HD, it is essential to determine if the transplanted ENCCs differentiate normally in aganglionic gut. Therefore, we designed this study to investigate the impact of the environment of the recipient intestinal tract, at various sites of aganglionic gut, on the differentiation of transplanted ENCCs.

Methods

ENCCs were isolated from Sox10 Venus transgenic (Tg) mouse gut on embryonic day 18.5 (E18.5) and neurospheres (NS) were generated. Then, NS were transplanted into aganglionic KO and wildtype (WT) gut that had been transected just distal to the ENCC wavefront (KO-wf: n = 6, WT: n = 7), and into distal KO gut transected at a site equivalent to that of the WT (KO-d: n = 6) on E12.5. ENCC differentiation was evaluated using whole-mount immunohistochemistry with Tuj-1 (neuronal marker) and GFAP (glial marker) antibodies.

Results

The transplanted ENCCs migrated to form the myenteric and submucosal plexus in all groups. The ratio of the area of Tuj-1-positive cells/GFAP-positive cells in migrated cells in the recipient gut was found to be significantly lower in KO-d compared to KO-wf and WT, while there was no significant difference between KO-wf and WT groups. This suggests that neuronal/glial differentiation was decreased in KO-d compared to that in KO-wf and WT groups.

Conclusion

Our study highlights the differences in ENCC differentiation depending on the site of transplantation. To further develop cell therapy for HD, it is important to consider the impact of the recipient intestinal environment on transplanted ENCCs.

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Titel: The impact of the recipient intestinal site on the differentiation of transplanted enteric neural crest cells
verfasst von: Nana Nakazawa-Tanaka
Naho Fujiwara
Katsumi Miyahara
Chihiro Akazawa
Masahiko Urao
Atsuyuki Yamataka
Publikationsdatum: 01.12.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: Pediatric Surgery International / Ausgabe 1/2023
Print ISSN: 0179-0358
Elektronische ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-023-05587-8

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The impact of the recipient intestinal site on the differentiation of transplanted enteric neural crest cells