Articulo

Cell Tissue Res (2011) 344:217–225 DOI 10.1007/s00441-011-1130-9

REGULAR ARTICLE

Evidence for neural progenitor cells in the human adult enteric nervous system
Gaetano Azan & Walter C. Low & Gwen Wendelschafer-Crabb & Sayeed Ikramuddin & William R. Kennedy

Received: 11 August 2010 / Accepted: 12 January 2011 / Published online: 3 March 2011 # Springer-Verlag 2011

Abstract Putativeneural 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 inthe 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/nestinnegative neuronal cells within ganglia, we observed two other types of cells: (1) cells in which PGP 9.5 and nestin
The authors thank the Juvenile Diabetes Research Foundation forsupporting research on the enteric nervous system. G. Azan : G. Wendelschafer-Crabb : W. R. Kennedy (*) Department of Neurology, University of Minnesota Medical School, Minneapolis, MN 55455, USA e-mail: kenne001@umn.edu S. Ikramuddin Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA W. C. Low Department of Neurosurgery, University of Minnesota Medical School,Minneapolis, MN 55455, USA W. C. Low Graduate Program in Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA W. C. Low Stem Cell Institute, University of Minnesota Medical School, Minneapolis, MN 55455, USA

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 cellpopulation 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. Keywords Enteric nervous system . Neural crest . Protein gene product 9.5 . Nestin . Neural progenitor cells . Human

Introduction The enteric nervous system (ENS) controls secretion, absorption, motility, blood flow, and theimmune response within the gastrointestinal (GI) tract by a series of interconnected ganglia of enteric neurons and glial cells that are located in the submucosal plexus and myenteric plexus (Furness 2000). Neurons and glial cells of the ENS are derived from stem cells in the neural crest, a transient structure present during embryologic development (Dupin et al. 2006). Neural crest stem cellsare multipotent cells with the capacity to self-renew, proliferate, and differentiate into neurons and glial cells (Stemple and Anderson 1992). Under the influence of differentiation and migration factors, neural crest stem cells give rise, within the gut, to neural progenitor cells (NPC) that have limited proliferative and self-renewal capacity (Lendahl et al. 1990; Messam et al. 2000). Neuralcrest stem cells were initially identified by their co-expression of the low affinity nerve growth factor receptor (p75) and the intermediate filament protein nestin (Stemple and Anderson 1992). NPCs are distinguished by their co-expression of nestin and PGP 9.5 (Chalazonitis et al. 1998; Messam et al. 2000; Rauch et al. 2006a, b; Silva et al. 2008).

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Cell Tissue Res (2011) 344:217–225NPCs persist in the ENS in young adult rodents (Kruger et al 2002). In tissue culture experiments of embryonic mouse ENS, dividing enteric progenitor cells form neurospheres that can be maintained for several months and, when provided with optimal conditions, differentiate into neurons or glial cells (Schäfer et al. 2003). Cultures of neural tissue derived from post-natal to adult human and rodent...