Transplantation of embryonic neuroectodermal progenitor cells into the site of a photochemical lesion: Immunohistochemical and electrophysiological analysis

GFP labeled/NE‐4C neural progenitor cells cloned from primary neuroectodermal cultures of p53− mouse embryos give rise to neurons when exposed to retinoic acid in vitro. To study their survival and differentiation in vivo, cells were transplanted into the cortex of 6‐week‐old rats, 1 week after the induction of a photochemical lesion or into noninjured cortex. The electrophysiological properties of GFP/NE‐4C cells were studied in vitro (8–10 days after differentiation induction) and 4weeks after transplantation using the whole‐cell patch‐clamp technique, and immunohistochemical analyses were carried out. After transplantation into a photochemical lesion, a large number of cells survived, some of which expressed the astrocytic marker GFAP. GFP/GFAP‐positive cells, with an average resting membrane potential (Vrest) of −71.9 mV, displayed passive time‐ and voltage‐independent K+ currents and, additionally, voltage‐dependent A‐type K+ currents (KA) and/or delayed outwardly rectifying K+ currents (KDR). Numerous GFP‐positive cells expressed NeuN, βIII‐tubulin, or 68 kD neurofilaments. GFP/βIII‐tubulin‐positive cells, with an average Vrest of −61.6 mV, were characterized by the expression of KA and KDR currents and tetrodotoxin‐sensitive Na+ currents. GFP/NE‐4C cells also gave rise to oligodendrocytes, based on the detection of oligodendrocyte‐specific markers. Our results indicate that GFP/NE‐4C neural progenitors transplanted into the site of a photochemical lesion give rise to neurons and astrocytes with membrane properties comparable to those transplanted into noninjured cortex. Therefore, GFP/NE‐4C cells provide a suitable model for studying neuro‐ and gliogenesis in vivo. Further, our results suggest that embryonic neuroectodermal progenitor cells may hold considerable promise for the repair of ischemic brain lesions. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006