Development of iPSC-induced Neural Crest Cells and Enteric Neural Crest Stem Cells in the Gut Following Transplantation
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AbstractHirschsprung’s disease is a neurocristopathy resulting from incomplete colonisation of the embryonic gut by neural crest cells and characterised by congenital enteric aganglionosis. Failure of relaxation in the aganglionic segment results in a functional obstruction and megacolon. Current definitive surgical treatment is associated with a significant risk of long-term complications with adverse psychosocial effects, particularly fecal incontinence. Cell therapy aiming at regenerating the enteric neurons in the aganglionic segment may be a promising alternative to surgery. Enteric neural crest stem cells (ENCSCs) isolated from embryos and neural crest cells (NCCs) induced from induced pluripotent stem cells (iPSCs) both possess neuronal differentiation potential and may be feasible cell types for transplantation.
In this study we aimed to compare the integration, migration and neuronal differentiation of these two cell types upon ex vivo and in vivo transplantation. Neurospheres generated from ENCSCs or single iPSC-induced NCCs (iNCCs) in suspension were transplanted to the wall of ganglionic mouse hindgut explants cultured ex vivo and the ganglionic distal descending colon of postnatal mice in vivo.
Upon ex vivo transplantation, ENCSCs migrated out from neurospheres and morphologically integrated well within the endogenous enteric nervous system (ENS) of the hindgut explant, whereas many iNCCs displayed morphological characteristics of cell death, with no evidence of extensive migration and integrated poorly. However, surviving ENCSCs and iNCCs demonstrated differentiation into TuJ1+ neuronal cells.
Upon in vivo transplantation, both cell types similarly were capable of differentiation into TuJ1+ cells. ENCSCs migrated extensively to form a network of branching fibres resembling the ENS located mainly between the longitudinal and circular muscle layers. Comparatively, iNCC survival was low, without extensive migration and integration.
Our results indicate ENCSCs are likely to possess a better ability to form enteric neurons than iNCCs within the developing and postnatal distal colon.
All Author(s) ListAllan LUI, Yuzhe NIU, Wood Yee CHAN
Name of Conference18th International Congress of Developmental Biology
Start Date of Conference18/06/2017
End Date of Conference22/06/2017
Place of ConferenceSingapore
Country/Region of ConferenceSingapore
LanguagesEnglish-United Kingdom

Last updated on 2018-26-04 at 16:58