Abstract: The present invention provides a clinically applicable method of stem cell transplantation that facilitates engraftment and reconstitutes immunocompetence of the recipient without requiring radiotherapy or chemotherapy, and without development of GVHD or graft rejection. Aspects of the present invention are based on the discovery that the depletion of the endogenous stem cell niche facilitates efficient engraftment of stem cells into that niche. In particular, the present invention combines the use of selective ablation of endogenous stem cells with a combination of antibodies specific for CD117, and agents that modulate immunoregulatory signaling pathways, e.g. agonists of immune costimulatory molecules, in combination with the administration to the recipient of exogenous stem cells, resulting in efficient, long-term engraftment, even in immunocompetent recipients.

Abstract: Methods are provided for treating a subject with a therapeutic dose of anti-CD47 agent by administering a primer agent prior to administering a therapeutically effective dose of an anti-CD47 agent to the subject.

Abstract: Methods are provided for treating a subject for an infection by a pathogen expressing a CD47-like mimic protein on its surface.

Abstract: GABRR1 is shown to be expressed on subsets of hematopoietic stem cells (HSCs) and megakaryocyte progenitors (MkPs). Inhibition of GABRR1 inhibits MkP differentiation and reduction of platelet numbers in blood. Overexpression of GABRR1 or treatment with agonists significantly promotes MkP generation and growth of megakaryocytes.

Abstract: Markers of acute myeloid leukemia stem cells (AMLSC) are identified. The markers are differentially expressed in comparison with normal counterpart cells, and are useful as diagnostic and therapeutic targets.

Abstract: Methods, compositions, and kits for producing functional blood vessels, and progenitors thereof are provided. Human disorders of the vascular system are treated by reconstitution of functional vessels in vivo through co-transplantation with supporting niche stromal cells for treatment of ischemic injury in the peripheral limbs and heart. The cell populations of the invention, when engrafted into a recipient, anastomose with host vasculature and regenerate functional blood vessels.

Abstract: An effective combined dose of an anti-CD47 agent and an anti-TNF? agent is administered to the subject in a dose and for a period of time effective to stabilize, prevent or reduce atherosclerotic plaque in the individual.

Abstract: Methods are provided for treatment of cutaneous T cell lymphoma with an effective dose of an anti-CD47 agent, optionally combined an additional anti-cancer agent.

Abstract: Prolonged exposure of CD8+ T cells to antigenic stimulation leads to a state of diminished function, termed exhaustion; during exhaustion there is a subset of functional CD8+ T cells defined by surface expression of SIRP(alpha) protein. On SIRP+ CD8+ T cells, expression of coinhibitmy receptors is counterbalanced by expression of co-stimulatory receptors and it is only these SIRP+ cells that actively proliferate, transcribe IFNg and show cytolytic activity. Therapeutic blockade of PD-L1 or other inhibitory receptors to reinvigorate exhausted CD8+ T cells expands the cytotoxic subset of SIRP+ CD8+ T cells.

Abstract: Methods are provided for treating a subject with for an intracellular pathogen infection, by administering an agent that reduces the binding of CD47 on a infected cell to SIRP? on a host phagocytic cell, in an effective dose for increasing the phagocytosis of infected cells.

Abstract: Compositions and methods are provided for treating fibrosis in a mammal by administering a therapeutic dose of a pharmaceutical composition.

Abstract: Methods and kits are provided for determining whether an individual is responsive to therapeutic CD47 blockade. Specifically, the disclosure provides methods of determining whether a cell or cell population is responsive to therapeutic CD47 blockade, the method comprising: assaying a cell sample from an individual to determine (a) the level of expression of signal regulatory protein alpha (SIRPalpha) on phagocytic immune cells, or (b) the genotype of the individual at a nucleotide polymorphism (SNP) associated with SIRPalpha expression. Further disclosed are SNPs associated with SIRPalpha expression.

Abstract: High affinity SIRP-? reagent are provided, which (i) comprise at least one amino acid change relative to the wild-type protein; and (ii) have an increased affinity for CD47 relative to the wild-type protein. Compositions and methods are provided for modulating phagocytosis in a mammal by administering a therapeutic dose of a pharmaceutical composition comprising a high affinity SIRP? reagent, which blocks the physiological binding interaction between SIRP? and its ligand CD47.

Abstract: An effective combined dose of an anti-CD47 agent and an anti-TNF agent is administered to the subject in a dose and for a period of time effective to stabilize, prevent or reduce atherosclerotic plaque in the individual.

Abstract: Methods are provided for targeting cells for depletion, including without limitation cancer cells, in a regimen comprising contacting the targeted cells with a combination of agents, including (i) an agent that blockades CD47 activity; and (ii) an antibody that specifically binds to EGFR. In some embodiments the cancer cells have a mutated form of one or more of KRAS, NRAS or BRAF. The level of depletion of the targeted cell is enhanced relative to a regimen in which a single agent is used; and the effect may be synergistic relative to a regimen in which a single agent is used.

Abstract: Compositions and methods are provided for diagnosis of infections. The patterns of antibody isotype, subtype and glycosylation provide for a signature pattern that can identify infective agents and patient response to infection. Patients likely to benefit from therapeutic intervention can be discriminated from patients that have a low probability of responsiveness. Therapies are also provided.

Abstract: Markers of acute myeloid leukemia stem cells (AMLSC) are identified. The markers are differentially expressed in comparison with normal counterpart cells, and are useful as diagnostic and therapeutic targets.

Abstract: The invention provides genetically modified hematopoietic stem or progenitor cells (HSPCs) and methods of using the HSPCs in stem cell replacement therapy. The HSPCs are genetically modified to express a receptor conferring a selective advantage on the introduced cells relative to endogenous HSPCs or a control HSPCs without the modification. The presence of such a receptor provides resistance to an immunotherapy regime used for eliminating endogenous HSPCs.

Abstract: Methods are provided for treating a subject with for an intracellular pathogen infection, by administering an agent that reduces the binding of CD47 on a infected cell to SIRP? on a host phagocytic cell, in an effective dose for increasing the phagocytosis of infected cells.

Abstract: Methods are provided herein for determining and administering optimized dosing of therapeutic anti-D47 agents, in a schedule that provides safe escalation of dose while achieving a therapeutic level in a clinically effective period of time. The methods can comprise the steps of clearance, escalation, and maintenance. In one embodiment the dosing regimen administers an initial (i) sub-therapeutic dose of an anti-CD47 agent or (ii) a cytoreductive therapy to achieve a safe level of circulating tumor cells for subsequent treatment (clearance); escalating the dose of an anti-CD47 agent until a therapeutic dose is reached (escalation); and maintaining the therapeutic dose for a period of time sufficient to reduce tumor cells in the bone marrow of the patient (maintenance). In an alternative dosing regimen, a patient determined to have a safe level of circulating tumor cells at presentation is treated by the steps of escalation and maintenance without initial clearance.