Live Imaging of Mouse Endogenous Neural Progenitors Migrating in Response to an Induced Tumor

Abstract

Adult neurogenesis is restricted to specific brain regions. Although involved in the continuous supply of interneurons for the olfactory function, the role of neural precursors in brain damage-repair remains an open question. Aiming to in vivo identify endogenous neural precursor cells migrating towards a brain damage site, the monoclonal antibody Nilo2 recognizing cell surface antigens on neuroblasts, was coupled to magnetic glyconanoparticles (mGNPs). The Nilo2-mGNP complexes allowed, by magnetic resonance imaging in living animals, the in vivo identification of endogenous neural precursors at their niche, as well as their migration to a lesion site (induced brain tumor), which was fast (within hours) and orderly. Interestingly, the rapid migration of neuroblasts towards a damage site is a characteristic that might be exploited to precisely localize early damage events in neurodegenerative diseases. In addition, it might facilitate the study of regenerative mechanisms through the activation of endogenous neural cell precursors. A similar approach, combining magnetic glyconanoparticles linked to appropriate antibodies could be applied to flag other small cell subpopulations within the organism, track their migration, localize stem cell niches, cancer stem cells or even track metastatic cells.

A mosaic world: puzzles revealed by adult neural stem cell heterogeneity

“…Radial glia in zebrafish can migrate long distances to lesioned areas, and neuronal subtypes generated under injury can differ from those produced constitutively . Similarly, migration of some neural progenitors to tumor/inflammatory sites has been observed in the adult mouse brain …”

Recent advances in biosensing using magnetic glyconanoparticles

“…3). The carboxyl groups available on the surface of the glycoMNPs can be used as anchoring points for further functionalization to yield (immuno)fluorescent glycoMNPs [28][29][30][31][32].…”

“…In vivo MRI with glycoMNPs has been used to detect diseases [38], track the migration of endogenous neuronal stem cells in response to an induced tumour [31] or track stem cells [ 77]. For instance, unfractioned-heparin-coated superparamagnetic iron oxide nanoparticles were used to detect human mesenchymal stem cells, which are considered to be good candidates in regenerative medicine [77].…”

In vivoimaging of endogenous neural stem cells in the adult brain

“…Alternatively, ferritin can be introduced into proliferating (stem) cells using viral vectors, rendering them detectable for MRimaging [63,64] . Recent progress in this field has also been made by the development of a monoclonal antibody binding to neural precursor cells, coupled to magnetic glyconanoparticles allowing for their detection by MRI [65] .While these approaches are quite promising to track eNSCs in individual experimental animals, a major disadvantage of those in vivo-labeling approaches is the lack of applicability in human beings due to the invasiveness of the labeling procedure.…”