NSCs implanted at various intracranial sites distant from main
tumor bed migrate through normal adult tissue toward glioma cells.
(A and B) Same hemisphere but
behind tumor (Paradigm 2). Shown here is a section through
the tumor from an adult nude mouse 6 days after NSC implantation caudal
to tumor. In A (as per the schematic, a coned down view
of a tumor populated as pictured under low power in Figs.
2A and 3 A and B),
note X-Gal+ blue NSCs interspersed among dark neutral
red+ tumor cells. (B) High power view of
NSCs in juxtaposition to islands of tumor cells. (C–H)
Contralateral hemisphere (Paradigm 3). (C–E) As
indicated on the schematic, these panels are views through the corpus
callosum (“c”) where β-gal+ NSCs (red cells,
arrows) are seen migrating from their site of implantation on one side
of the brain toward tumor on the other. Two representative NSCs
indicated by arrows in C are viewed at higher
magnification in D and E, respectively,
to visualize the classic elongated morphology and leading process of a
migrating neural progenitor oriented toward its target. In
F, β-gal+ NSCs (red) are “homing in”
on the GFP+ tumor (green) having migrated from the other
hemisphere. In G, and magnified further in
H, the X-Gal+ blue NSCs (arrows) have now
actually entered the neutral red+ tumor (arrowheads) from
the opposite hemisphere. (I and J)
Intraventricular (Paradigm 4). Shown here is a section through the
brain tumor of an adult nude mouse 6 days following NSC injection into
the contralateral cerebral ventricle. In I, as per the
schematic, blue X-Gal+ NSCs are distributed within the
neutral red+ main tumor bed (edge delineated by
arrowheads). At higher power in J, the NSCs are in
juxtaposition to migrating islands of red glioblastoma cells.
Fibroblast control cells never migrated from their injection site in
any paradigm. All X-Gal-positivity was corroborated by anti-β-gal
immunoreactivity. (Scale bar: A, 20 μm, and applies to
C; B, 8 μm, 14 μm in D
and E, 30 μm in F and G,
15 μm in H, 20 μm in I, and 15 μm
in J.)