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 homogeneouspopulation of multipotential precursor cells from mammalian embryonicneuroepithelium (CNS stem cells) can be expanded up to 109 fold in culturewhile maintaining their multipotential capacity to differentiate into neurons,oligodendrocytes, and astrocytes. Chemically defined conditions are presentedthat enable a large number of neurons, up to 50 % of the expanded cells, to bederived from the stem cells. In addition, four factors -- PDGF, CNTF, LIF andT3 -- have been identified, which, individually, generate significantly higherproportion of neurons, astrocytes, or oligodendrocytes. These definedprocedures permit a large-scale preparation of the mammalian CNS stem cells,neurons, astrocytes, and oligodendrocytes under chemically defined conditionswith efficiency and control. The present invention also reveals in vitrocultures of region-specific, terminally differentiated, mature neurons derivedfrom cultures of mammalian multipotential CNS stem cells and an in vitroprocedure by which the differentiated neurons may be generated.