You are hereMay 31, 2021 | Neural Crest Stem Cells
Enteric Nervous System Regeneration with Pre-Migratory Neural Crest Stem Cells
Review of "Premigratory neural crest stem cells generate enteric neurons populating the mouse colon and regulating peristalsis in tissue‐engineered intestine" from STEM CELLS Translational Medicine by Stuart P. Atkinson
Stem cell‐based replacement therapy represents an exciting treatment option for Hirschsprung's disease , which results from the absence of the neural crest cell-derived enteric nervous system within the distal large intestine . A recent STEM CELLS Translational Medicine study from researchers led by Yi Dong (East China Normal University, Shanghai), Wei Chen, and Jinfa Tou (Zhejiang University, Hangzhou, China) sought to explore the potential of multipotent mouse pre-migratory neural crest stem cells (pNCSCs)  to reconstitute the enteric nervous system after transplantation into the adult mouse intestine and establish neuron‐dependent bowel motility . Excitingly, Yuan et al. now report that non-enteric NCSCs may represent an exciting alternative treatment option for enteric nervous system regeneration in patients suffering from conditions such as Hirschsprung's disease.
The authors first isolated pNCSCs from trunk-level neural tubes derived from mouse embryos employing a previously established procedure  and confirmed their i) identity through immunostaining for expected markers (Nestin, P75, AP2, and SOX10), ii) multipotent differentiation potential, and iii) ability to generate peripheral neurons that displayed an appropriate morphology and marker expression profile. The study then demonstrated that pNCSCs transplanted into the external muscle layer survived, migrated, and efficiently differentiated into fully functional enteric neurons that successfully integrated into the neural network of the adult mouse large intestine over a period of two months.
Their subsequent analysis evaluated mature tissue‐engineered intestinal tissue, formed through a combination of pNCSCs and human intestinal organoids implanted into the subrenal capsule of nude mice, in the hope of proving the ability of pNCSC-derived neurons to mediate peristalsis [6, 7]. Overall, pNCSCs efficiently differentiated into neurons within human intestinal organoids, while analysis of motility suggested that they integrated and then mediated neuron‐dependent peristalsis within this tissue‐engineered intestine, providing evidence for their potential to induce gut motility.
Overall, these findings suggest that pNCSCs that lack any induction by intestinal microenvironmental cues can integrate within the mouse large intestine and mediate gut motility, thereby suggesting their application in the regeneration of the enteric nervous system in patients suffering from conditions such as Hirschsprung's disease. In addition, the authors note that easier-to-isolate non-enteric adult NCSCs could share developmental origins with pNCSCs and, therefore, may represent potential candidates for novel enteric nervous system regeneration strategies.
For more on the potential of pre-migratory neural crest stem cells and novel treatment options for enteric nervous system disorders, stay tuned to the Stem Cells Portal!
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