Effects of tissue age, presence of neurones and endothelin-3 on the ability of enteric neurone precursors to colonize recipient gut: implications for cell-based therapies
Article first published online: 23 SEP 2009
© 2009 Blackwell Publishing Ltd
Neurogastroenterology & Motility
Volume 22, Issue 3, pages 331–e86, March 2010
How to Cite
Hotta, R., Anderson, R. B., Kobayashi, K., Newgreen, D. F. and Young, H. M. (2010), Effects of tissue age, presence of neurones and endothelin-3 on the ability of enteric neurone precursors to colonize recipient gut: implications for cell-based therapies. Neurogastroenterology & Motility, 22: 331–e86. doi: 10.1111/j.1365-2982.2009.01411.x
- Issue published online: 5 FEB 2010
- Article first published online: 23 SEP 2009
- Received: 17 August 2009 Accepted for publication: 31 August 2009
- enteric nervous system;
- enteric neuropathy;
- Hirschsprung’s disease;
- neural crest
Background Most enteric neurones arise from neural crest cells that originate in the post-otic hindbrain, and migrate into and along the developing gastrointestinal tract. There is currently great interest in the possibility of cell therapy to replace diseased or absent enteric neurones in patients with enteric neuropathies, such as Hirschsprung’s disease. However, it is unclear whether neural crest stem/progenitor cells will be able to colonize colon (i) in which the mesenchyme has differentiated into distinct layers, (ii) that already contains enteric neurones or (iii) that lacks a gene expressed by the gut mesenchyme, such as endothelin-3 (Et-3).
Methods Co-cultures were used to examine the ability of enteric neural crest-derived cells (ENCCs) from E11.5 mouse gut to colonize a variety of recipient hindguts.
Key Results Enteric neural crest-derived cells migrated and gave rise to neurones in E14.5 and E16.5 aneural colon in which the external muscle layers had differentiated, but they did not migrate as far as in younger colon. There was no evidence of altered ENCC proliferation, cell death or neuronal differentiation in older recipient explants. Enteric neural crest-derived cells failed to enter most recipient E14.5 and E16.5 colon explants already containing enteric neurones, and the few that did showed very limited migration. Finally, ENCCs migrated a shorter distance and a higher proportion expressed the pan-neuronal marker, Hu, in recipient E11.5 Et-3−/− colon compared to wild-type recipient colon.
Conclusions & Inferences Age and an absence of Et-3 from the recipient gut both significantly reduced but did not prevent ENCC migration, but the presence of neurones almost totally prevented ENCC migration.