A fusion polypeptide, comprising an inclusion body tag fused to at least one polypeptide of interest, is provided. The inclusion body tag comprises an inclusion body forming (IBF) amino acid sequence selected from X.sub.14X.sub.15AX.sub.17X.sub.18X.sub.19GLTVA GMLG and sequences having at least 71% identity thereto. Also provided are inclusion bodies comprising the fusion polypeptide, as well as nucleic acids, expression vectors, host cells and methods for its production.

Described is a method of producing a storage stable autologous composition comprising regenerative growth factors and cytokines obtained from platelets. The method comprises the steps of collecting or providing blood from a mammal; delivering the blood to a receptacle; centrifuging the blood to separate a platelet rich plasma component from the blood; collecting the platelet rich plasma component; passing the platelet rich plasma component through a small pore filter to produce the storage stable autologous composition comprising regenerative growth factors and cytokines derived from platelets; and collecting the storage stable autologous composition. The storage stable autologous composition retains regenerative biological activity for up to at least nine months when stored in a frozen state. Also described is a storage stable autologous composition comprising regenerative growth factors and cytokines obtained from platelets produced by the method as described.

The present invention relates to methods, kits and compositions for expansion of embryonic hematopoietic stem cells and providing hematopoietic function to human patients in need thereof. In one aspect, it relates to kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGF pathway. Also provided herein are methods for expanding embryonic hematopoietic stem cells using kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGF pathway. The embryonic hematopoietic stem cells expanded using the disclosed kits, compositions and methods include cells derived from an embryo (e.g., aorta-gonad-mesonephros region of the embryo), embryonic stem cells, induced pluripotent stem cells, or reprogrammed cells of other types. The present invention also relates to administering the embryonic hematopoietic stem cells expanded using a combination of a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGF pathway to a patient for short-term and/or long-term in vivo repopulation benefits.

Genetically modified non-human animals expressing human EPO from the animal genome are provided. Also provided are methods for making non-human animals expressing human EPO from the non-human animal genome, and methods for using non-human animals expressing human EPO from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human erythropoiesis and erythrocyte function; in modeling human pathogen infection of erythrocytes; in in vivo screens for agents that modulate erythropoiesis and/or erythrocyte function, e.g. in a healthy or a diseased state; in in vivo screens for agents that are toxic to erythrocytes or erythrocyte progenitors; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on erythrocytes or erythrocyte progenitors; in in vivo screens of erythrocytes or erythrocyte progenitors from an individual to predict the responsiveness of an individual to a disease therapy.

A genetically-modified, immunodeficient mouse is provided along with methods of use, wherein the mouse includes (a) a nucleotide sequence encoding human stem cell factor (hSCF); (b) a nucleotide sequence encoding human granulocyte-macrophage colony-stimulating factor (hGM-CSF); (c) a nucleotide sequence encoding human interleukin-3 (hIL-3); and (d) a nucleotide sequence encoding human colony-stimulating factor 1 (hCSF1), wherein each of the nucleotide sequences is operably linked to a promoter, and wherein the genetically-modified, immunodeficient mouse expresses hSCF, hGM-CSF, hIL-3, and hCSF1, wherein the genetically-modified, immunodeficient mouse allows engraftment of human hematopoietic stem cells along with engraftment of human-patient derived tumor xenografts and/or human tumor cell lines to enable in vivo investigation of the interactions between the human immune system and human cancer.

A mouse with a humanization of the miL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mII2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/II2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.

Disclosed are cysteine variants of interleukin-11 (IL-11) and methods of making and using such proteins in therapeutic applications.

Described herein are compositions and methods targeting IL-3 signaling for reducing Alzheimer's disease (AD)-related pathology.

The present invention relates to a human CD123-targeting chimeric receptor ligand, comprising an IL-3 molecule-based CD123 binding domain, a transmembrane region, and an intracellular signaling domain. The present invention provides a T cell modified by the human CD123-targeting chimeric receptor ligand and capable of specifically binding with CD123 on tumor cell surfaces, thereby having specific cytotoxicity on tumor cells. The present invention further relates to an application of the human CD123-targeting chimeric receptor ligand and an immune effector cell thereof in preparing an anti-tumor immunotherapy drug.

Disclosed are cysteine variants of interleukin-11 (IL-11) and methods of making and using such proteins in therapeutic applications.