Evidence for neural progenitor cells in the human adult enteric nervous system
Putative neural stem cells have been identified within the enteric nervous system (ENS) of adult rodents and cultured from human myenteric plexus. We conducted studies to identify neural stem cells or progenitor cells within the submucosa of adult human ENS. Jejunum tissue was removed from adult human subjects undergoing gastric bypass surgery. The tissue was immunostained, and confocal images of ganglia in the submucosal plexus were collected to identify protein gene product 9.5 (PGP 9.5) - immunoractive neurons and neuronal progenitor cells that coexpress PGP 9.5 and nestin. In addition to PGP-9.5-positive/nestin-negative neuronal cells within ganglia, we observed two other types of cells: (1) cells in which PGP 9.5 and nestin were co-localized, (2) cells negative for both PGP 9.5 and nestin. These observations suggest that the latter two types of cells are related to a progenitor cell population and are consistent with the concept that the submucosa of human adult ENS contains stem cells capable of maintenance and repair within the peripheral nervous system.
KeywordsEnteric nervous system Neural crest Protein gene product 9.5 Nestin Neural progenitor cells Human
- Chalazonitis A, Rothman TP, Chen J, Gershon MD (1998) Age-dependent differences in the effects of GDNF and NT-3 on the development of neurons and glia from neural crest-derived precursors immunoselected from the fetal rat gut: expression of GFRalpha-1 in vitro and in vivo. Dev Biol 204:385–406PubMedCrossRefGoogle Scholar
- Faure C, Chalazonitis A, Rheaume C, Bouchard G, Gopalan Sampathkumar S, Yarema KJ, Gershon MD (2007) Gangliogenesis in the enteric nervous system: roles of the polysialylation of the neural cell adhesion molecule and its regulation by bone morphogenetic protein-4. Dev Dyn 236:44–59PubMedCrossRefGoogle Scholar
- Metzger M, Bareiss PM, Danker T, Wagner S, Hennenlotter J, Guenther E, Obermayr F, Stenzl A, Koenigsrainer A, Skutella T, Just L (2009b) Expansion and differentiation of neural progenitors derived from the human adult enteric neurvous system. Gastroenterology 137:2063–2073PubMedCrossRefGoogle Scholar
- Quiñones-Hinojosa A, Sanai N, Soriano-Navarro M, Gonzalez-Perez O, Mirzadeh Z, Gil-Perotin S, Romero-Rodriguez R, Berger MS, Garcia-Verdugo JM, Alvarez-Buylla (2006) Cellular composition and cytoarchitecture of the adult human subventricular zone: a niche of neural stem cells. J Comp Neurol 494:415–434PubMedCrossRefGoogle Scholar
- Sakurai M, Ayukawa K, Setsuie R, Nishikawa K, Hara Y, Ohashi H, Nishimoto M, Abe T, Kudo Y, Sekiguchi M, Sato Y, Aoki S, Noda M, Wada K (2006) Ubiquitin C-terminal hydrolase L1 regulates the morphology of neural progenitor cells and modulates their differentiation. J Cell Sci 119:162–167PubMedCrossRefGoogle Scholar