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Erschienen in: Pediatric Surgery International 1/2023

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

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

Erschienen in: Pediatric Surgery International | Ausgabe 1/2023

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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.
Literatur
1.
Zurück zum Zitat Furness JB (2012) The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol 9(5):286–294CrossRefPubMed Furness JB (2012) The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol 9(5):286–294CrossRefPubMed
2.
Zurück zum Zitat 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 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
3.
Zurück zum Zitat 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 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
4.
Zurück zum Zitat 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 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
5.
Zurück zum Zitat 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 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
6.
Zurück zum Zitat 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 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
7.
Zurück zum Zitat 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 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
8.
Zurück zum Zitat 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 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
9.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Zuber SM, Grikscheit TC (2019) Stem cells for babies and their surgeons: The future is now. J Pediatr Surg 54(1):16–20CrossRefPubMed Zuber SM, Grikscheit TC (2019) Stem cells for babies and their surgeons: The future is now. J Pediatr Surg 54(1):16–20CrossRefPubMed
12.
Zurück zum Zitat Iannaccone PM et al (1994) Pluripotent embryonic stem cells from the rat are capable of producing chimeras. Dev Biol 163(1):288–292CrossRefPubMed Iannaccone PM et al (1994) Pluripotent embryonic stem cells from the rat are capable of producing chimeras. Dev Biol 163(1):288–292CrossRefPubMed
13.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Thomson JA et al (1998) Embryonic stem cell lines derived from human blastocyst. Science 282(5391):1145–1147CrossRefPubMed Thomson JA et al (1998) Embryonic stem cell lines derived from human blastocyst. Science 282(5391):1145–1147CrossRefPubMed
17.
Zurück zum Zitat Kanda A et al (2012) Establishment of ES cells from inbred strain mice by dual inhibition (2i). J Reprod 58(1):77–83 Kanda A et al (2012) Establishment of ES cells from inbred strain mice by dual inhibition (2i). J Reprod 58(1):77–83
18.
Zurück zum Zitat Bondurand N, Sham MH (2013) The role of SOX10 during enteric nervous system development. Dev Biol 382(1):330–343CrossRefPubMed Bondurand N, Sham MH (2013) The role of SOX10 during enteric nervous system development. Dev Biol 382(1):330–343CrossRefPubMed
19.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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
23.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Ying QL, Smith AG (2003) Defined conditions for neural commitment and differentiation. Methods Enzymol 365:327–341CrossRefPubMed Ying QL, Smith AG (2003) Defined conditions for neural commitment and differentiation. Methods Enzymol 365:327–341CrossRefPubMed
26.
Zurück zum Zitat 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 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.
Zurück zum Zitat Bondurand N, Kobetz A, Pingault V (1998) Expression of the SOX10 gene during human development. FEBS Lett 432(3):168–172CrossRefPubMed Bondurand N, Kobetz A, Pingault V (1998) Expression of the SOX10 gene during human development. FEBS Lett 432(3):168–172CrossRefPubMed
28.
Zurück zum Zitat 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 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.
Zurück zum Zitat Obermayr F, Seitz G (2018) Recent developments in cell-based ENS regeneration – a short review. Innov Surg Sci 3(2):93–99PubMedPubMedCentral Obermayr F, Seitz G (2018) Recent developments in cell-based ENS regeneration – a short review. Innov Surg Sci 3(2):93–99PubMedPubMedCentral
30.
Zurück zum Zitat Mueller JL, Goldstein AM (2022) The science of Hirschsprung disease: what we know and where we are headed. Semin Pediatr Surg 31(2):151157CrossRefPubMed 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.
Zurück zum Zitat Rajabzadeh N, Fathi E, Farahzadi R (2019) Stem cell-based regenerative medicine. Stem Cell Investig 18(6):19CrossRef Rajabzadeh N, Fathi E, Farahzadi R (2019) Stem cell-based regenerative medicine. Stem Cell Investig 18(6):19CrossRef
32.
Zurück zum Zitat 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 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
Metadaten
Titel
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
verfasst von
Naho Fujiwara
Katsumi Miyahara
Nana Nakazawa-Tanaka
Yoshie Oishi
Chihiro Akazawa
Norihiro Tada
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/s00383-022-05318-5

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