In VivoTracking of Neural Progenitor Cell Migration to Glioblastomas

Abstract

The ability to noninvasively track the migration, engraftment, and proliferation of neural progenitor cells (NPCs) has significant clinical and research implications. The purpose of our study was to explore the macroscopic migratory capabilities of NPCs toward brain tumors after implantation into nude mice. We stably transfected C17.2 NPCs with the firefly luciferase gene (F-luc) and implanted cells into (1) the contralateral brain parenchyma (2 x 10(6) cells), (2) the ventricles (2 x 10(6) cells), (3) the vasculature (1 x 10(5) cells), or (4) the intraperitoneal cavity (5 x 10(6) cells) of mice bearing intracranial gliomas (Gli36). Using serial bioluminescence imaging, migration of parenchymally injected cells was observed across the corpus callosum, first detected at 1 week, with maximal density at the tumor site 2-3 weeks after implantation. Similar patterns were also observed with intraventricular injections; however, tumors were populated earlier, presumably because of the shorter distance to travel. Intravenous injections resulted in more modest tumoral NPC populations, whereas virtually no cells could be identified in tumors after intraperitoneal injection. These results confirm the migratory capability of NPCs over considerable distances and their preferential accumulation in brain tumors on CNS rather than peripheral injection.

Bioluminescence imaging of Smad signaling in living mice shows correlation with excitotoxic neurodegeneration

“…Bioluminescence imaging has been used recently for the study of gene expression in transgenic mice that express luciferase reporter genes under control of various promoters or transcription factor binding sites (35)(36)(37)(38). In the brain, bioluminescence has been used mainly to track and quantify luciferase-tagged tumor cells (39)(40)(41)(42) or to trace migration of neural progenitor cells (43,44). One study used glial fibrillary acidic protein (GFAP)-luciferase transgenic mice to demonstrate activation of the reporter after injury, but no correlation with neuronal injury or degeneration was demonstrated (38).…”

Molecular imaging of gene therapy for cancer

“…Recently we have explored the macroscopic migratory capabilities of NPCs towards experimental tumors following implantation into nude mice at distant sites in the brain. 87 A line of NPCs stably expressing Fluc was either implanted into the brain parenchyma or administered via intraparenchymal and intraventricular injections into mice bearing intracranial gliomas. Using serial BLI, migration of NPCs implanted in the brain was observed across the corpus callosum towards the tumor, with movement first being detected at 1 week and maximal density within the tumor site observed at 2-3 weeks after implantation 87 ( Figure 6).…”

“…87 A line of NPCs stably expressing Fluc was either implanted into the brain parenchyma or administered via intraparenchymal and intraventricular injections into mice bearing intracranial gliomas. Using serial BLI, migration of NPCs implanted in the brain was observed across the corpus callosum towards the tumor, with movement first being detected at 1 week and maximal density within the tumor site observed at 2-3 weeks after implantation 87 ( Figure 6). These results confirm the histologically documented migratory capability of NPCs over considerable distances and their preferential accumulation in brain tumors upon CNS injection.…”

Molecular optical imaging: Applications leading to the development of present day therapeutics

“…Recently, we have explored the macroscopic migratory capabilities of NPCs toward experimental tumors after implantation into nude mice at distant sites in the brain. 52 A line of NPCs stably expressing Fluc was either implanted into the brain parenchyma or administered via intraparenchymal and intraventricular injections into mice bearing intracranial gliomas. Using serial BLI, migration of NPCs implanted in the brain was observed across the corpus callosum toward the tumor, with movement first being detected at 1 week and maximal density within the tumor site observed at 2-3 weeks after implantation (FIG.…”