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Updated: Jun 17, 2026
A Quantitative Cell Migration Assay for Murine Enteric Neural Progenitors
Published on: September 18, 2013
Human enteric nervous system progenitor transplantation improves functional responses in Hirschsprung disease
Benjamin Jevans1,2, Fay Cooper3,4, Yuliia Fatieieva5
1Stem Cells and Regenerative Medicine, UCL GOS Institute of Child Health, London, UK.
Insights
Human pluripotent stem cell-derived enteric nervous system progenitors show potential for treating Hirschsprung disease (HSCR). Transplanted cells integrated into HSCR colon tissue, restoring motor function and improving contractility.
Area of Science:
- Stem cell biology
- Developmental biology
- Gastroenterology
Background:
- Hirschsprung disease (HSCR) is a congenital disorder caused by incomplete enteric nervous system (ENS) colonization.
- Current treatment involves surgical resection, often leading to lifelong complications.
- Alternative therapies, such as stem cell transplantation, are needed.
Purpose of the Study:
- To generate and characterize enteric nervous system (ENS) progenitors from human pluripotent stem cells (hPSCs).
- To evaluate the therapeutic potential of hPSC-derived ENS progenitors in Hirschsprung disease (HSCR) models.
Main Methods:
- hPSCs were differentiated into ENS progenitors using an accelerated protocol.
- Cells were characterized using single-cell RNA sequencing, protein analysis, and calcium imaging.
- Transplantation into ex vivo HSCR colon tissue was assessed using organ bath contractility and electrical stimulation.
Main Results:
- The protocol yielded high-purity ENS progenitors with characteristic markers.
- Transplanted hPSC-derived ENS progenitors integrated, migrated, and differentiated into neurons and glia within HSCR colon tissue.
- Transplanted tissue exhibited significantly enhanced basal contractility and response to electrical stimulation.
Conclusions:
- hPSC-derived ENS progenitors can successfully repopulate and functionally improve human HSCR colon tissue.
- This study demonstrates a promising new avenue for HSCR regenerative therapy.
Objective:
Hirschsprung disease (HSCR) is a severe congenital disorder affecting 1:5000 live births. HSCR results from the failure of enteric nervous system (ENS) progenitors to fully colonise the gastrointestinal tract during embryonic development. This leads to aganglionosis in the distal bowel, resulting in disrupted motor activity and impaired peristalsis. Currently, the only viable treatment option is surgical resection of the aganglionic bowel. However, patients frequently suffer debilitating, lifelong symptoms, with multiple surgical procedures often necessary. Hence, alternative treatment options are crucial. An attractive strategy involves the transplantation of ENS progenitors generated from human pluripotent stem cells (hPSCs).
Design:
ENS progenitors were generated from hPSCs using an accelerated protocol and characterised, in detail, through a combination of single-cell RNA sequencing, protein expression analysis and calcium imaging. We tested ENS progenitors' capacity to integrate and affect functional responses in HSCR colon, after ex vivo transplantation to organotypically cultured patient-derived colonic tissue, using organ bath contractility.
Results:
We found that our protocol consistently gives rise to high yields of a cell population exhibiting transcriptional and functional hallmarks of early ENS progenitors. Following transplantation, hPSC-derived ENS progenitors integrate, migrate and form neurons/glia within explanted human HSCR colon samples. Importantly, the transplanted HSCR tissue displayed significantly increased basal contractile activity and increased responses to electrical stimulation compared with control tissue.
Conclusion:
Our findings demonstrate, for the first time, the potential of hPSC-derived ENS progenitors to repopulate and increase functional responses in human HSCR patient colonic tissue.
