MAINTENANCE OF GENOMIC STABILITY IN CULTURED STEM CELLS

摘要

The present application relates to methods and compositions for the generation of therapeutic cells having reduced incidence of karyotypic abnormalities. In several embodiments cardiac stem cells are cultured in an antioxidant-supplemented media that reduces levels of reactive oxygen species, but does not down regulate DNA repair mechanisms. In several embodiments, physiological oxygen concentrations are used during culture in order to increase the proliferation of stem cells, decrease the senescence of the cells, decrease genomic instability, and/or augment the functionality of such cells for cellular therapies.

主权项

1. A method for reducing the incidence of karyotypic abnormalities in cardiac stem cells for use in the repair or regeneration of cardiac tissue, the method comprising:
isolating cardiac stem cells, wherein said cells are isolated from healthy mammalian non-embryonic cardiac tissue; and culturing said isolated stem cells in a culture media supplemented with an antioxidant composition, wherein said antioxidant composition comprises at least one peptide antioxidant and at least one non-peptide antioxidant, wherein said at least one peptide antioxidant is present in a concentration ranging from about 0.1 to 200 μM, wherein said at least at least one non-peptide antioxidant is present in a concentration ranging from about 0.1 to 200 μM, wherein said antioxidant composition reduces reactive oxygen species to a level which decreases oxidative-stress induced DNA damage, wherein said reduction in reactive oxygen species does not significantly reduce markers of DNA repair mechanisms, wherein said reduction in reactive oxygen species does not significantly induce markers of DNA damage in said cardiac stem cells, and wherein the balance of reduced reactive oxygen species, non-reduced DNA repair mechanisms and non-induction of DNA damage reduces the incidence of karyotypic abnormalities in said cardiac stem cells.