ArticlePloS one2016
In Vivo Transplantation of Enteric Neural Crest Cells into Mouse Gut; Engraftment, Functional Integration and Long-Term Safety.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Management and outcomes for long-segment Hirschsprung disease: A systematic review from the APSA Outcomes and Evidence Based Practice Committee.Journal of pediatric surgery · 2021Pooled it
- Embryonic Gut Enteric Neural Crest Cells Derived Neurospheres.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Enteric nervous system as a therapeutic target in gastrointestinal disorders.World journal of gastrointestinal pharmacology and therapeutics · 2025Article
- GFRA4 improves the neurogenic potential of enteric neural crest stem cells via hedgehog pathway.Pediatric research · 2024Article
- Updates and Challenges in ENS Cell Therapy for the Treatment of Neurointestinal Diseases.Biomolecules · 2024Review
- Intra-arterial delivery of neurospheres into isolated perfused porcine colons: a proof of concept.Biology methods & protocols · 2024Article
- Enteric neurospheres retain the capacity to assemble neural networks with motile and metamorphic gliocytes and ganglia.Stem cell research & therapy · 2023Article
- Transplanted ENSCs form functional connections with intestinal smooth muscle and restore colonic motility in nNOS-deficient mice.Stem cell research & therapy · 2023Article
- Harnessing the Power of Enteric Glial Cells' Plasticity and Multipotency for Advancing Regenerative Medicine.International journal of molecular sciences · 2023Review
- Cardiac Neural Crest and Cardiac Regeneration.Cells · 2022Review
- Review
- Human Pluripotent Stem Cell-Based Models for Hirschsprung Disease: From 2-D Cell to 3-D Organoid Model.Cells · 2022Review
- Enteric neurosphere cells injected into rectal submucosa might migrate caudorostrally to reconstitute enteric ganglia along the entire length of postnatal colon.Stem cell research & therapy · 2022Article
- Article
- Dynamic integration of enteric neural stem cells in ex vivo organotypic colon cultures.Scientific reports · 2021Article
- Premigratory neural crest stem cells generate enteric neurons populating the mouse colon and regulating peristalsis in tissue-engineered intestine.Stem cells translational medicine · 2021Article
- Neural crest-like stem cells for tissue regeneration.Stem cells translational medicine · 2021Review
- Combined treatment with enteric neural stem cells and chondroitinase ABC reduces spinal cord lesion pathology.Stem cell research & therapy · 2021Article
- Comment on a recent genetic study on the risk profile of Hirschsprung's disease from a pediatric surgeon's perspective.Annals of translational medicine · 2020Article
- Retinoic Acid Accelerates the Specification of Enteric Neural Progenitors from In-Vitro-Derived Neural Crest.Stem cell reports · 2020Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
objectivesEnteric neuropathies are severe gastrointestinal disorders with unsatisfactory outcomes. We aimed to investigate the potential of enteric neural stem cell therapy approaches for such disorders by transplanting mouse enteric neural crest cells (ENCCs) into ganglionic and aganglionic mouse gut in vivo and analysing functional integration and long-term safety.
designNeurospheres generated from yellow fluorescent protein (YFP) expressing ENCCs selected from postnatal Wnt1-cre;R26R-YFP/YFP murine gut were transplanted into ganglionic hindgut of wild-type littermates or aganglionic hindgut of Ednrbtm1Ywa mice (lacking functional endothelin receptor type-B). Intestines were then assessed for ENCC integration and differentiation using immunohistochemistry, cell function using calcium imaging, and long-term safety using PCR to detect off-target YFP expression.
resultsYFP+ ENCCs engrafted, proliferated and differentiated into enteric neurons and glia within recipient ganglionic gut. Transplanted cells and their projections spread along the endogenous myenteric plexus to form branching networks. Electrical point stimulation of endogenous nerve fibres resulted in calcium transients (F/F0 = 1.16 ± 0.01;43 cells, n = 6) in YFP+ transplanted ENCCs (abolished with TTX). Long-term follow-up (24 months) showed transplanted ENCCs did not give rise to tumours or spread to other organs (PCR negative in extraintestinal sites). In aganglionic gut ENCCs similarly spread and differentiated to form neuronal and glial networks with projections closely associated with endogenous neural networks of the transition zone.
conclusionsTransplanted ENCCs successfully engrafted into recipient ganglionic and aganglionic gut showing appropriate spread, localisation and, importantly, functional integration without any long-term safety issues. This study provides key support for the development and use of enteric neural stem cell therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.