Isolation, propagation, and directed differentiation of stem...

C - Chemistry – Metallurgy – 12 – N

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C12N 5/0797 (2010.01) C12N 5/074 (2010.01) G01N 33/50 (2006.01) G01N 33/94 (2006.01) A61K 35/12 (2006.01)

Patent

CA 2257068

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.

L'invention concerne un procédé in vitro permettant d'amplifier jusqu'à 10?9¿ fois dans une culture une population homogène de cellules précurseurs à potentialités multiples provenant du neuroépithélium embryonnaire mammifère (cellules souches du système nerveux central), tout en conservant leur capacité multipotentielle à se différencier en neurones, en oligodendrocytes et en astrocytes. Elle concerne également des conditions déterminées chimiquement permettant d'obtenir à partir de ces cellules souches un nombre important de neurones, 50 % maximum des cellules amplifiées. De plus, quatre facteurs -PDGF, CNTF, LIF et T3- ont été identifiés et génèrent individuellement des proportions considérablement plus élevées de neurones, d'astrocytes et d'oligodendrocytes. Ces procédés permettent de préparer, de façon efficace et à une échelle importante, des cellules souches du système nerveux central mammifère, des neurones, des astrocytes et des oligodendrocytes dans des conditions déterminées chimiquement. L'invention concerne également des cultures in vitro de neurones matures, spécifiques à une région, à différenciation terminale, provenant de cultures de cellules souches du système nerveux central mammifère, ainsi qu'un procédé in vitro permettant de générer ces neurones différenciés.

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