Isolation, characterization and infection of pigtailed macaque fetal neural progenitor and mesenchymal stem cells

The HIV infected pediatric population is disproportionately affected by HIV progressive encephalopathy (HIV-PE), characterized by failure to reach developmental milestones, physiological and mood disorders and death or the similar, though less progressive, HIV static encephalitis (HIV-SE). HIV encephalitis in adults is characterized by neurodegeneration with loss of neurons and accompanying cognitive and motor deficits. Since macaque neural development closely parallels that of human brain development, and neural progenitor cells (NPCs) are thought to play a critical role in replacement of dead neurons and probably other neural cells, we isolated and characterized NPCs from pigtailed macaques to determine whether they can be differentiated into neurons and glia. We also asked whether NPCs and astrocytes derived from NPCs were susceptible to infection by simian immunodeficiency viruses (SIV).; We isolated NPCs from the brains of 50 to 55 day fetal macaques and showed that the earliest progenitors had characteristic NPC morphology and expressed the neural progenitor markers nestin and Musashi-1. We also demonstrated that these NPCs could be reliably differentiated into pure cultures of astrocytes and neurons.; We further demonstrated that both the NPCs and the NPC-derived astrocytes could be infected by several strains of SIV. SIV showed a viral infection pattern similar to that seen in human NPCs infected with HIV: p27 production only during the first week of infection, but levels of gag RNA in cell-free supernatant as high as 5x107 copy equivalents per mL continuously from day 3 to day 30 post-infection. These data suggest that pigtailed macaque NPCs behave, look, and develop like their human counterparts, and are likewise susceptible to infection with their respective lentiviruses. These NPCs can now be used to expand our understanding of the pathogenesis of HIV in the developing brain and the extent to which NPCs can replace neural cells or neural cell function lost during HIV infection of the adult brain.