Top

Published in:

01-12-2023 | Original Article

Differentiation of enteric neural crest cells transplanted from SOX10-Venus mouse embryonic stem cells into the gut of the endothelin receptor B null mouse model

Authors: Naho Fujiwara, Katsumi Miyahara, Nana Nakazawa-Tanaka, Yoshie Oishi, Chihiro Akazawa, Norihiro Tada, Atsuyuki Yamataka

Published in: Pediatric Surgery International | Issue 1/2023

Abstract

Purpose

Failure of enteric neural crest-derived cells (ENCCs) to correctly colonize the embryonic gut results in Hirschsprung’s disease (HD). Embryonic stem cells (ESCs) have the potential to differentiate into all tissue-specific cells and lineages, including ENCCs. We investigated the cellular differentiation of ESCs from Sox10-Venus⁺ mice into both control and endothelin receptor-B knockout (Ednrb KO) mouse gut to assess each region.

Methods

We established ESCs from Sox10-Venus ⁺ mice. These cells were cultured for 2 days, then selected and co-cultured with either a dissociated control or Sox10-Venus ^– Ednrb KO mouse gut (both small intestine and colon) on embryonic day (E) 13.5. Four days later, cells were immunolabeled for Tuj1 and visualized using confocal microscopy.

Results

Confocal microscopy revealed that transplanted Sox10-Venu ⁺ cells from ESCs migrated extensively within the host gut. Moreover, Tuj1-positive neurites were detected in the transplanted ESCs. Tuj1 expression was significantly decreased in aganglionic HD colon compared to controls (p < 0.05) and the HD small intestine (p < 0.05).

Conclusions

This study demonstrated that an appropriate host environment is crucial for normal and complete colonization of the gut. Further investigations are required to confirm whether modifying this environment can improve the results of this model.

Furness JB (2012) The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol 9(5):286–294CrossRefPubMed

Burns AJ (2005) Migration of neural crest-derived enteric nervous system precursor cells to and within the gastrointestinal tract. Int J Dev Biol 49(2–3):143–150CrossRefPubMed

Goldstein AM, Hofstra RM, Burns AJ (2013) Building a brain in the gut: development of the enteric nervous system. Clin Genet 83(4):307–316CrossRefPubMed

Granström AL, Danielson J, Husberg B et al (2015) Adult outcomes after surgery for Hirschsprung’s disease: evaluation of bowel function and quality of life. J Pediatr Surg 50(11):1865–1869CrossRefPubMed

Zimmer J, Tomuschat C, Puri P (2016) Long-term results of transanal pull-through for Hirschsprung’s disease: a meta-analysis. Pediatr Surg Int 32(8):743–749CrossRefPubMed

Sood S, Lim R, Collins L et al (2018) The long-term quality of life outcomes in adolescents with Hirschsprung disease. J Pediatr Sur 53(12):2430–2434CrossRef

Burns AJ et al (2016) White paper on guidelines concerning enteric nervous system stem cell therapy for enteric neuropathies. Dev Biol 417(2):229–251CrossRefPubMedPubMedCentral

Hotta R, Cheng L, Graham HK et al (2016) Delivery of enteric neural progenitors with 5-HT4 agonist-loaded nanoparticles and thermosensitive hydrogel enhances cell proliferation and differentiation following transplantation in vivo. Biomaterials 88:1–11CrossRefPubMedPubMedCentral

Lindley RM, Hawcutt DB, Connell MG et al (2009) Properties of secondary and tertiary human enteric nervous system neurospheres. J Pediatr Surg 44(6):1249–1255CrossRefPubMed

10.

Fattahi F, Steinbeck JA, Kriks S et al (2016) Deriving human ENS lineages for cell therapy and drug discovery in Hirschsprung disease. Nature 531(7592):105–109CrossRefPubMedPubMedCentral

11.

Zuber SM, Grikscheit TC (2019) Stem cells for babies and their surgeons: The future is now. J Pediatr Surg 54(1):16–20CrossRefPubMed

12.

Iannaccone PM et al (1994) Pluripotent embryonic stem cells from the rat are capable of producing chimeras. Dev Biol 163(1):288–292CrossRefPubMed

13.

Giles JR, Yang X, Mark W et al (1993) Pluripotency of cultured rabbit inner cell mass cells detected by isozyme analysis and eye pigmentation of fetuses following injection into blastocysts or morulae. Mol Reprod Dev 36(2):130–138CrossRefPubMed

14.

Notarianni E, Laurie S, Moor M et al (1990) Maintenance and differentiation in culture of pluripotential embryonic cell lines from pig blastocysts. J Reprod Fertil Suppl 41:51–56PubMed

15.

Handyside A, Hooper ML, Kaufman MH (1987) Towards the isolation of embryonal stem cell lines from the sheep. Rouxs Arch Dev Biol 196(3):185–219CrossRefPubMed

16.

Thomson JA et al (1998) Embryonic stem cell lines derived from human blastocyst. Science 282(5391):1145–1147CrossRefPubMed

17.

Kanda A et al (2012) Establishment of ES cells from inbred strain mice by dual inhibition (2i). J Reprod 58(1):77–83

18.

Bondurand N, Sham MH (2013) The role of SOX10 during enteric nervous system development. Dev Biol 382(1):330–343CrossRefPubMed

19.

Shibata S, Yasuda A, Renault-Mihara F et al (2010) Sox10-Venus mice: a new tool for real-time labeling of neural crest lineage cells and oligodendrocytes. Mol Brain 3:31CrossRefPubMedPubMedCentral

20.

Fujiwara N, Miyahara K, Nakazawa-Tanaka N et al (2016) Altered differentiation of enteric neural crest-derived cells from endothelin receptor-B null mouse model of Hirschsprung’s disease. Pediatr Surg Int 32(12):1095–1101CrossRefPubMed

21.

Buehr M et al (2003) Genesis of embryonic stem cells. Philos Trans R Soc Lond B Biol Sci 358(1436):1397–1402CrossRefPubMedPubMedCentral

22.

Ying QL, Wray J, Nichols J et al (2008) The ground state of embryonic stem cell self-renewal. Nature 453(7194):519–523CrossRefPubMedPubMedCentral

23.

Fujiwara N, Miyahara K, Nakazawa-Tanaka N et al (2022) In vitro investigation of the differentiation of enteric neural crest-derived cells following transplantation of aganglionic gut in a mouse model. Pediatr Surg Int 38(5):755–759CrossRefPubMed

24.

Kawaguchi J, Nichols J, Gierl MS et al (2010) Isolation and propagation of enteric neural crest progenitor cells from mouse embryonic stem cells and embryos. Development 137:693–704CrossRefPubMedPubMedCentral

25.

Ying QL, Smith AG (2003) Defined conditions for neural commitment and differentiation. Methods Enzymol 365:327–341CrossRefPubMed

26.

Aoki Y, Saint-Germain N, Gyda M (2003) Sox10 regulates the development of neural crest-derived melanocytes in Xenopus. Dev Biol 259(1):19–33CrossRefPubMed

27.

Bondurand N, Kobetz A, Pingault V (1998) Expression of the SOX10 gene during human development. FEBS Lett 432(3):168–172CrossRefPubMed

28.

Stavely R, Bhave S, Ho WLN (2021) Enteric mesenchymal cells support the growth of postnatal enteric neural stem cells. Stem Cells 39(9):1236–1252CrossRefPubMed

29.

Obermayr F, Seitz G (2018) Recent developments in cell-based ENS regeneration – a short review. Innov Surg Sci 3(2):93–99PubMedPubMedCentral

30.

Mueller JL, Goldstein AM (2022) The science of Hirschsprung disease: what we know and where we are headed. Semin Pediatr Surg 31(2):151157CrossRefPubMed

31.

Rajabzadeh N, Fathi E, Farahzadi R (2019) Stem cell-based regenerative medicine. Stem Cell Investig 18(6):19CrossRef

32.

Hagl CI, Rauch U, Klotz M (2012) The microenvironment in the Hirschsprung’s disease gut supports myenteric plexus growth. Int J Colorectal Dis 27(6):817–829CrossRefPubMed

Title: Differentiation of enteric neural crest cells transplanted from SOX10-Venus mouse embryonic stem cells into the gut of the endothelin receptor B null mouse model
Authors: Naho Fujiwara
Katsumi Miyahara
Nana Nakazawa-Tanaka
Yoshie Oishi
Chihiro Akazawa
Norihiro Tada
Atsuyuki Yamataka
Publication date: 01-12-2023
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Surgery International / Issue 1/2023
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-022-05318-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Differentiation of enteric neural crest cells transplanted from SOX10-Venus mouse embryonic stem cells into the gut of the endothelin receptor B null mouse model

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2023

Nephron sparing surgery outcomes in Wilms’ tumor: is it ready for primetime?

Parental perceptions and experiences of care in the surgical neonatal intensive care unit

The advantages of duct-to-duct biliary reconstruction in pediatric living donor liver transplantation

Cardiac anomalies in children with congenital duodenal obstruction: a systematic review with meta-analysis

Novel hypothesis on the origin of gastroschisis?

The role of distance between upper and lower esophageal pouches to predict the possibility of delayed repair in children with isolated esophageal atresia