Multipotent stem/progenitor cells with similar properties arise from two neurogenic regions of adult human brain

Recent in vitro studies have shown that the periventricular subependymal zo ne (SEZ) of the rodent brain is capable of de novo generation of neurons an d glia. There is less information available on neurogenesis in the adult hu man brain, and no study has shown the clonal generation of neurons and glia from in vitro-generated "neurospheres." Here we describe the isolation of proliferative stem/progenitor cells within neurospheres from two different regions, the SEZ and the hippocampus, from surgical biopsy specimens of adu lt (24-57 years) human brain. Using light and electron microscopy; immunocy tochemistry for a variety of neuronal, glial, and developmental (including extracellular matrix; ECM) markers; and the reverse transcriptase polymeras e chain reaction to demonstrate different gene transcripts found in neurosp heres, it is shown that the adult human brain harbors a complex population of stem/progenitor cells that can generate neuronal and glial progeny under particular in vitro growth conditions. These methods also show that these neurospheres contain both neurons and glia and demonstrate regional similar ities at the mRNA level, indicating common stem/progenitor cell types withi n two different neurogenic regions of the adult human brain. In addition to the synthesis of developmentally regulated molecules such as the ECM prote in tenascin-C, a variety of other genes (e.g., Pax 6) and proteins (e.g., B cl-2) involved in cell survival and differentiation are expressed by adult human brain neurospheres. (C) 1999 Academic Press.