Enteric mesenchymal cells support the growth of postnatal enteric neural stem cells

This study identifies that mesenchymal non ‐neural crest‐derived cells (NNCDCs) from the postnatal intestine act as supporting cells to enteric neural crest‐derived cells (ENCDCs) and enhances ENCDC expression of neural stem cell markers. These properties can be leveraged to expand ENCDCs for their therapeutic application as demonstrat ed by successful engraftment and differentiation after transplantation in a mouse model of Hirschsprung disease. AbstractInterplay between embryonic enteric neural stem cells (ENSCs) and enteric mesenchymal cells (EMCs) in the embryonic gut is essential for normal development of the enteric nervous system. Disruption of these interactions underlies the pathogenesis of intestinal aganglionosis in Hirschsprung disease (HSCR). ENSC therapy has been proposed as a possible treatment for HSCR, but whether the survival and development of postnatal ‐derived ENSCs similarly rely on signals from the mesenchymal environment is unknown and has important implications for developing protocols to expand ENSCs for cell transplantation therapy. Enteric neural crest‐derived cells (ENCDCs) and EMCs were cultured from the small intestine ofWnt1 ‐Rosa26‐tdTomato mice. EMCs promoted the expansion of ENCDCs 9.5 ‐fold by inducing ENSC properties, including expression ofNes,Sox10,Sox2, andNgfr. EMCs enhanced the neurosphere ‐forming ability of ENCDCs, and this persisted after withdrawal of the EMCs. These effects were mediated by paracrine factors and...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Tissue ‐Specific Stem Cells Source Type: research