Methods for modulating hematopoiesis and vascular growth
AssigneePresident and Fellows of Harvard College
InventorsMARGARET H. BARON, SARAH M. FARRINGTON, MARIA BELAUSSOFF
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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.
Claims56
A method of stimulating a population of undifferentiated mesodermally derived cells to undergo at least one of hematopoiesis and vascular growth;
- comprising:
- (a) selecting a compound that is functionally equivalent to a gene product expressed in an embryo's extraembryonic tissue;
- (b) causing the compound to access the cells, so as to stimulate the cells to undergo at least one hematopoiesis and vascular growth.
A method of treating developmental errors in vascular growth or hematopoiesis in an embryo in utero, comprising:
- (a) selecting an effective dose of a compound that is functionally equivalent to a gene product expressed in an extraembryonic tissue;
- and
- (b) causing the compound to access a population of embryonic cells in vivo, so as to stimulate the cells to undergo at least one of hematopoiesis and vascular growth.
A method of treating a subject suffering from an abnormal number of erythroid cells, comprising:
- (a) selecting an effective dose of a compound that is functionally equivalent to a gene product expressed in an extraembryonic tissue;
- and
- (b ) causing the compound to access a population of hematopoietic stem cells over an effective time so as to modulate the number of cells undergoing at least one of proliferation or hematopoiesis.
A method of treating a subject suffering from an ischemia in tissues, comprising:
- (a) selecting an effective dose of a compound that is functionally equivalent to a gene product expressed in an extraembryonic tissue;
- and
- (b) administering the compound to the ischemic site over an effective time so as to stimulate vascular growth within the ischemic tissues.
A method of treating abnormally enhanced vascular growth in a subject, comprising:
- (a) selecting an effective dose of a hedgehog compound capable of inhibiting the activity of a gene product expressed in an extraembryonic tissue;
- and
- (b) administering the compound to the subject over an effective time so as to inhibit abnormally enhanced vascular growth.
An in vitro assay for determining the activity of a compound capable of modulating hematopoiesis or vascular growth, comprising:
- (a) selecting a population of cells from a tissue derived from a fertilized egg of a mammal, wherein the population of cells is deficient in blood formation as detectable by the absence of a predetermined marker;
- and
- (b) adding an agent to the population of cells so as to reverse the deficiency.
An assay for determining the activity of a compound capable of modulating hematopoiesis or vascular growth, comprising:
- (a) selecting a first transgenic animal carrying a marker:ε-globin hybrid gene;
- wherein the ε-globin gene is capable of expression at least up to 15.5 dpc.;
- (b) mating the first transgenic animal to a second animal that is similarly transgenic;
- (c) isolating an embryo from the mating during the gestation period;
- and
- (d) determining the effect of the compound on the stimulation of hematopoiesis and vascular growth in the isolated embryo by measuring marker expression.
Dependencies are inferred from the claim text.