Methods of using hedgehog proteins to modulate hematopoiesis and vascular growth
AssigneePresident and Fellows of Harvard College
InventorsMargaret H. Baron, Sarah M. Farrington, Maria Belaoussoff
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Abstract
This application pertains to methods and compositions that modulate proliferation and/or differentiation of undifferentiated mesodermally-derived cells so as to have an effect on at least one of vascular growth and hematopoiesis.
Claims80
A method of stimulating a population of undifferentiated mammalian mesodermally derived cells to undergo hematopoiesis, comprising contacting the cells with an amount of a hedgehog compound effective to stimulate the cells to undergo hematopoiesis, wherein the hedgehog compound comprises a polypeptide sequence at least 80% identical to a sequence selected from SEQ ID NO:
- 34, SEQ ID NO:
- 35, SEQ ID NO:
- 36, SEQ ID NO:
- 37, SEQ ID NO:
- 38, SEQ ID NO:
- 39, SEQ ID NO:
- 40, or a fragment of said polypeptide sequence which polypeptide sequence or fragment of said polypeptide sequence binds to patched and induces cells to undergo hematopoiesis.
A method of stimulating hematopoiesis in an animal, comprising administering to the animal an effective amount of a hedgehog compound comprising a polypeptide sequence at least 80% identical to a sequence selected from SEQ ID NO:
- 34, SEQ ID NO:
- 35, SEQ ID NO:
- 36, SEQ ID NO:
- 37, SEQ ID NO:
- 38 SEQ ID NO:
- 39, SEQ ID NO:
- 40, or a fragment of said polypeptide sequence which polypeptide sequence or fragment binds to patched and induces cells to undergo hematopoiesis.
A method of stimulating a population of undifferentiated mammalian mesodermally derived cells to undergo hematopoiesis, comprising contacting the cells with an effective amount of a hedgehog compound comprising a polypeptide sequence of SEQ ID NO:
- 41, SEQ ID NO:
- 42, or a fragment of said polypeptide sequence which polypeptide sequence or fragment thereof binds to patched and induces cells to undergo hematopoiesis.
A method of stimulating hematopoiesis in an animal, comprising administering to the animal an effective amount of a hedgehog compound comprising a polypeptide sequence of SEQ ID NO:
- 41, SEQ ID NO:
- 42, or a fragment of said polypeptide sequence which polypeptide sequence or fragment thereof binds to patched and induces cells to undergo hematopoiesis.
A method of stimulating a population of undifferentiated mammalian mesodermally derived cells to undergo hematopoiesis, comprising contacting the cells with an amount of a hedgehog compound effective to stimulate the cells to undergo hematopoiesis, wherein the hedgehog compound comprises a polypeptide sequence encoded by a nucleic acid which hybridizes under stringent conditions, including a wash step of 0.2×SSC at 65° C., to a nucleic acid sequence designated in one of SEQ ID Nos. 27-33, which polypeptide sequence binds to patched and induces cells to undergo hematopoiesis.
A method according to 32, wherein the cells comprise an embryonic explant culture.
A method of stimulating a population of undifferentiated mammalian mesodermally derived cells to undergo hematopoiesis, comprising contacting the cells with means for activating hedgehog signaling in an amount effective to stimulate the cells to undergo hematopoiesis.
A method according to 53, wherein the TGF-β polypeptide enhances the stimulation of hematopoiesis of the cells by more than the amount of stimulation of hematopoiesis resulting from administration of an identical amount of the TGF-β polypeptide in the absence of the means for activating hedgehog signaling.
A method of stimulating hematopoiesis in an animal, comprising administering to the animal means for activating hedgehog signaling in an amount effective to induce cells to undergo hematopoiesis.
A method of stimulating a population of undifferentiated mammalian mesodermally derived cells to undergo hematopoiesis, comprising contacting the cells with means for binding patched and thereby activating hedgehog signaling in an amount effective to induce cells to undergo hematopoiesis.
A method of stimulating hematopoiesis in an animal, comprising administering to the animal means for binding patched and thereby activating hedgehog signaling in an amount effective to induce cells to undergo hematopoiesis.
Dependencies are inferred from the claim text.