ISOLATION, PROPAGATION, AND DIRECTED DIFFERENTIATION OF STEM CELLS FROM CENTRAL NERVOUS SYSTEM OF MAMMALS

摘要

The present invention reveals an in vitro procedure by which an homogeneous population of multipotential precursor cells from mammalian embryonic neuroepithelium (CNS stem cells) can be expanded up to 109 fold in culture while maintaining their multipotential capacity to differentiate into neurons, oligodendrocytes, and astrocytes. Chemically defined conditions are presented that enable a large number of neurons, up to 50 % of the expanded cells, to be derived from the stem cells. In addition, four factors -- PDGF, CNTF, LIF and T3 -- have been identified, which, individually, generate significantly higher proportion of neurons, astrocytes, or oligodendrocytes. These defined procedures permit a large-scale preparation of the mammalian CNS stem cells, neurons, astrocytes, and oligodendrocytes under chemically defined conditions with efficiency and control. The present invention also reveals in vitro cultures of region-specific, terminally differentiated, mature neurons derived from cultures of mammalian multipotential CNS stem cells and an in vitro procedure by which the differentiated neurons may be generated.