Translational research and therapeutic applications of enteric neural crest stem cells
Neural Crest Stem Cells (NCSCs) or Neural Crest Cells (NCCs) are considered as one type of stem cells/neural progenitor cells. The main characteristics of this type of stem cells are listed as follows: (1) they are derived from the embryonic central nervous system; (2) they can migrate long distances to various locations of the body; and (3) just like other types of stem cells, they can differentiate into a wide variety of cells/tissues depending on their final locations. Hence they are ideal and suitable for the studies of cell migration, cell differentiation and also stem cell development.
The yolk sac membrane encloses a mouse embryo with a beating heart
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Currently, the migration and also differentiation of NCSCs in the embryonic gut are being examined in my studies using mouse and Xenopus embryos as experimental animals. These groups of embryonic stem cells are particularly focused on because they are related to a common congenital gastrointestinal mobility disease, namely Hirschsprung’s disease (i.e. congenital megacolon), in which enteric nerve cells are absent or reduced in numbers. Because of this absence or reduction of nerve cells, the motility (or peristalsis) of the colon becomes abnormal, and as a consequence, the intestinal content cannot be excreted properly but accumulated inside, resulting in a distended segment of the colon of varying lengths (i.e. megacolon).
To understand the pathogenesis of this disease, my studies aim to determine how abnormal migration and differentiation of NCSCs contribute to the defective development of the enteric nervous system and what factors and molecules are involved in the abnormal development of NCSCs leading to abnormal motility or peristalsis of the gut. In addition, the feasibility of transplanting different types of stem cells to the defective gut segment to rescue the abnormal development of enteric nerve cells is being explored. The stem cells under study include stem cells from the embryonic and neonatal gut, the neonatal skin and iPSCs (induced pluripotent cells from skin fibroblasts), and their differentiation under different experimental conditions are being examined.
Cell migrating away from a pelvic ganglion
DAY 4
Technique for organotypic culture of the embryonic gut ex vivo
Immunofluorescent staining of the embryonic hindgut
Ex-vivo tranplantation of GFP-labelled cells to an embryonic hindgut
Immunofluorescent staining of a rat adult myenteric plexus ganglion