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

Gema Elvira,Isabel García,Augusto Silva,Soledad Penadés,Manuel Desco,Marina Benito,Juan Gallo,Jose A Garcia-Sanz,Joseph Najbauer

doi:10.1371/journal.pone.0044466

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.

Highlights

In spite of new advances in understanding the biology of embryonic stem cells and induced pluripotent stem cells, tissuespecific stem cells remain the most promising cells for regenerative medicine, due to their ability to self-renew and differentiate into the distinct cell types that constitute a particular tissue
Nilo2 Coupled to Magnetic Nanoparticles Identified in vivo Neuroblasts in Neurogenic Niches The monoclonal antibody Nilo2, recently developed and characterized in our laboratory, was chosen for this study since it identifies, in living cells surface, antigens on subventricular zone (SVZ) neural precursors [35]
Double stainings revealed that Nilo2+ cells were positive for neuroblast markers and negative for neural stem cell markers (DCX+, PSANCAM+, GFAP2 or SOX22) (Figure 1A)

Summary

Introduction

In spite of new advances in understanding the biology of embryonic stem cells and induced pluripotent stem cells, tissuespecific stem cells remain the most promising cells for regenerative medicine, due to their ability to self-renew and differentiate into the distinct cell types that constitute a particular tissue. MRI combined with contrast agents has been widely used as a noninvasive technique to study cell migration of grafted cells with an efficient labeling without impairment on cell survival, proliferation, self-renewal or multipotency [34]. Taken together, these data suggest migration of neural cells to damage sites, without direct evidence for migration of any particular endogenous progenitor subpopulation, and allow envisaging the possibility that in response to brain damage there is neurogenesis in the adult brain

Methods

Results

Conclusion