Microglia, the primary immune cells of the brain, significantly influence the fate
of neurons after neural damage. Depending on the local environment, they exhibit a
wide range of phenotypes, including patrolling (naïve), proinflammatory, and anti-inflammatory
characteristics, which greatly affects neurotoxicity. Despite the fact that neural
progenitor cells (NPCs) and hippocampal neurons represent cell populations, which
play pivotal role in neural regeneration, interaction between microglia and these
cell types is poorly studied. In the present work, we investigated how microglial
cells affect the proliferation and neurite outgrowth of human stem cell-derived NPCs,
and how microglia stimulation with proinflammatory or anti-inflammatory agents modulates
this interaction. We found that naïve microglia slightly diminish NPC proliferation
and have no effect on neurite outgrowth. In contrast, proinflammatory stimulated microglia
promote both proliferation and neurite generation, whereas microglia stimulated with
anti-inflammatory cytokines augment neurite outgrowth leaving NPC proliferation unaffected.
We also studied how microglia influence neurite development and differentiation of
hippocampal dentate gyrus granule cells differentiated from NPCs. We found that proinflammatory
stimulated microglia inhibit axonal development but facilitate dendrite generation
in these differentiating neurons. Our results elucidate a fine-tuned modulatory effect
of microglial cells on cell types crucial for neural regeneration, opening perspectives
for novel regenerative therapeutic interventions.
