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AssigneesCalifornia Institute of Technology, National Institutes of Health
InventorsMarie Csete, John Doyle, Barbara J. Wold, Ron McKay, Lorenz Studer
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The present invention relates to the growth of cells in culture under conditions that promote cell survival, proliferation, and/or cellular differentiation. The present inventors have found that proliferation was promoted and apoptosis reduced when cells were grown in lowered oxygen as compared to environmental oxygen conditions traditionally employed in cell culture techniques. Further, the inventors found that differentiation of precursor cells to specific fates also was enhanced in lowered oxygen where a much greater number and fraction of dopaminergic neurons were obtained when mesencephalic precursors were expanded and differentiated in lowered oxygen conditions. Thus at more physiological oxygen levels the proliferation and differentiation of CNS precursors is enhanced, and lowered oxygen is a useful adjunct for ex vivo generation of specific neuron types. Methods and compositions exploiting these findings are described.
A method of increasing cell differentiation comprising culturing undifferentiated central nervous system (CNS) cells in low ambient oxygen conditions, wherein said low ambient oxygen conditions promotes the cellular differentiation of said neuronal cells.
A method of inhibiting apoptosis of a CNS cell in culture comprising growing said cell in low ambient oxygen conditions.
A method of increasing the expansion of a CNS cell in culture comprising growing said cell in low ambient oxygen, wherein said cell exhibit increased expansion in said low ambient oxygen as compared to growing said cell in 20% oxygen incubator conditions.
A method of increasing cell proliferation in culture comprising growing CNS cells in low ambient oxygen, wherein said growth in low ambient oxygen increases cell proliferation compared to growing said cells in 20% oxygen incubator conditions.
A method of preparing a cell for use against a neurodegenerative disorder comprising
A cell produced according to the method comprising obtaining a starting CNS cell and growing said cell in low ambient oxygen conditions wherein said conditions produce a differentiated neuronal cell.
A method of treating Parkinson's disease in a subject comprising:
Dependencies are inferred from the claim text.