Neural progenitors of the postnatal and adult mouse forebrain retain the ability to self-replicate, form neurospheres, and undergo multipotent differentiation in vivo

Somatic stem cells are reservoirs to replace lost cells or damaged tissue. Cells with neural stem cell (NSC) characteristics can be isolated from the postnatal mammalian brain into adulthood and expanded as neurospheres. We addressed the ability of these in vitro expanded putative NSCs to retain progenitor characteristics in vivo, in analogy to hematopoietic stem cells. When transplanted in utero, both postnatal and adult neural progenitors colonize host brains and contribute neurons and glia. In stark contrast to what has been reported when transplanted in postnatal hosts, epidermal growth factor-expanded cells also remain self-replicating and multipotent in vivo over many months and can be serially transplanted into multiple hosts. Surprisingly, embryonically transplanted NSCs remain in the neurogenic regions in adult hosts, where they express progenitor cell markers and continue to proliferate even after 6 months without tumor formation. These data indicate that spherogenic cells of the postnatal and adult mammalian brain retain their potential in vitro and in vivo throughout the life of the organism and beyond transplantation, which has important implications for cell replacement strategies.