Expansion of renewable stem cell populations
OwnerTony Peled, Avi Treves +1inventors
InventorsTony Peled, Avi Treves, Oren Rosen
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Abstract
Ex vivo and in vivo methods of expansion of renewable stem cells, expanded populations of renewable stem cells and their uses.
Claims24
A method of hematopoietic stem cell (HSC) transplantation or implantation comprising:
- (a) culturing hematopoietic stem cells ex-vivo in the presence of conditions allowing for HSC proliferation and, in the same culture medium, providing 0.1-20.0 mM exogenously added nicotinamide or nicotinamide analog, wherein culturing said HSC in said added nicotinamide or nicotinamide analog results in an expanded population of hematopoietic stem cells with an increased proportion of undifferentiated HSC as compared to HSC cultured in the presence of the same conditions allowing for HSC proliferation without exogenously added nicotinamide or nicotinamide analog;
- and
- (b) transplanting or implanting said stem cells to a recipient.
An isolated transplantable hematopoietic cell preparation comprising:
- an expanded population of hematopoietic stem cells propagated ex-vivo in the presence of conditions allowing for HSC proliferation and, in the same culture medium, providing 0.1-20.0 mM exogenously added nicotinamide or nicotinamide analog, wherein culturing said HSC in said added nicotinamide or nicotinamide analog results in an expanded population of hematopoietic stem cells with an increased proportion of undifferentiated HSC as compared to HSC cultured in the presence of the same conditions allowing for HSC proliferation without exogenously added nicotinamide or nicotinamide analog;
- and
- a pharmaceutically acceptable carrier.
A method of preserving stem cells comprising:
- isolating harvested stem cells;
- storing said isolated stem cells, wherein in at least one of said isolating and storing steps said cells are contacted with 0.1-20 mM of exogenously added nicotinamide or a nicotinamide analog selected capable of substantially inhibiting differentiation of said stem cells.
A stem cell collection/culturing bag supplemented with 1.0 to 20.0 Mm of nicotinamide or a nicotinamide analog selected capable of substantially inhibiting differentiation of said stem cells.
A stem cell separation and/or washing buffer supplemented with 1.0 to 20.0 Mm of nicotinamide or a nicotinamide analog selected capable of substantially inhibiting differentiation of said stem cells.
A method of genetically modifying hematopoietic stem cells with an exogene comprising:
- (a) culturing hematopoietic stem cells ex-vivo in the presence of conditions allowing for HSC proliferation and, in the same culture medium, providing 0.1-20.0 mM exogenously added nicotinamide or nicotinamide analog, wherein culturing said HSC in said added nicotinamide or nicotinamide analog results in an expanded population of hematopoietic stem cells with an increased proportion of undifferentiated HSC as compared to HSC cultured in the presence of the same conditions allowing for HSC proliferation without exogenously added nicotinamide or nicotinamide analog;
- and
- (b) genetically modifying said stem cells with the exogene.
A method of adoptive immunotherapy comprising:
- (a) culturing hematopoietic stem cells ex-vivo in the presence of conditions allowing for HSC proliferation and, in the same culture medium, providing 0.1-20.0 mM exogenously added nicotinamide or nicotinamide analog, wherein culturing said HSC in said added nicotinamide or nicotinamide analog results in an expanded population of hematopoietic stem cells with an increased proportion of undifferentiated HSC as compared to HSC cultured in the presence of the same conditions allowing for HSC proliferation without exogenously added nicotinamide or nicotinamide analog;
- and
- (b) transplanting said stem cells to the recipient.
Dependencies are inferred from the claim text.