Figure 6.

Grafts are Heteregenous in Composition and Contain Predominately Non-DA Neuronal Subtypes

(A) Immunohistochemistry for EGFP, NeuN, and FOXA2 at 28 weeks illustrates the relative contribution of DA neurons (EGFP⁺/NeuN⁺/FOXA2⁺) and non-DA neurons (NeuN⁺/GFP⁻) as well as ventralized (FOXA2⁺) cell types which included both neurons (NeuN⁺) and NeuN⁻, presumably immature, cell types (dashed lines approximate the graft-host border).

(B and C) The graft was highly immunoreactive for GABA (red), where human NCAM defines the graft (blue) and EGFP (green) is included to show DA neurons (B). Individual GABA neurons are difficult to resolve but can be delineated in the enlarged boxed area (C).

(D–L) Human-specific detection of NCAM in representative coronal sections (D) illustrates the overall extent of graft-derived fiber outgrowth, with prominent innervation of various host territories including, but not limited to: the frontal cortex contralateral (E) and ipsilateral (F) to the graft; lateral septal nuclei (G); perirhinal cortex (I); basolateral amygdala (J, contralateral hemisphere shown); and caudal aspects of the ventral hippocampus (L). Cells with glial morphology migrated extensively through host white matter tracts, particularly adjacent to the corpus callosum (H), and migrated long distances as far caudally as the midbrain (K).

Scale bars, 100 μm (A and B), 50 μm (C), 1 mm (D), 200 μm (E; applies to E–L).