This disclosure relates generally to methods for generating small hepatocyte progenitor cells (SHPCs) and hematopoietic progenitor cells (HPCs) from human embryonic stem cells, and hematopoietic progenitor cells from primary human endothelial cells and cell lines populations of small hepatocyte progenitor cells and hematopoietic progenitor cells, and uses thereof.

A non-human mammalian model for human diseases or disorders comprising a non-human neutrophil depleted mammalian host engrafted with a human skin equivalent (huSE) and human immune cells.

The present invention relates to a method of culturing primitive macrophages from stem cells. Specifically, the method comprises contacting and incubating stem cells with a serum-free culture media comprising a GSK3 inhibitor to differentiate stem cells into cell of the mesoderm lineage, contacting and incubating cells of the mesoderm lineage with a culture media comprising DKK1 to differentiate the cells into the hematopoietic lineage, maturing the cells of the hematopoietic lineage and contacting and incubating these cells with a culture media comprising M-CSF to drive differentiation into primitive-like macrophages. The invention also relates to a primitive-like macrophage, use of the primitive-like macrophage and a kit when used in the method of the invention.

Viral promoters and compositions and methods of use thereof are provided. Compositions include viruses with impaired ability to reactivate from latency, and pharmaceutical compositions and method of use thereof. The genome of the viruses include one or more mutations that reduce expression from one or more promoters that regulate expression of viral genes during reactivation from latency. The mutation(s) are typically in a region of the viral genome that includes (i) promoter elements of the iP1 promoter of human cytomegalovirus, or the sequence of another virus corresponding thereto (e.g., an iP1 promoter homolog); (ii) promoter elements of the iP2 promoter of human cytomegalovirus, or sequence of another virus corresponding thereto (e.g., an iP2 promoter homolog); or (iii) a combination thereof. In some embodiments the virus encodes one or more heterologous antigens. The viruses can be used as vaccines to induce prophylactic and therapeutic immune responses in subjects in need thereof.

The present invention relates to the use of immunoregulatory macrophages for treating diseases that are associated with pathological changes of the blood vessels. The present invention particularly relates to the use of immunoregulatory macrophages for treating micro- and macroangiopathies of the lower limbs. The invention furthermore relates to the use of immunoregulatory macrophages for promoting tissue remodelling to facilitate wound healing. Pharmaceutical compositions for use in the recited treatments are also disclosed which comprise the immunoregulatory macrophages.

The present invention provides modified monocytes, modified macrophages, pharmaceutical compositions comprising the modified monocytes or modified macrophages described herein and at least one pharmaceutically acceptable carrier or excipient. Uses of the modified monocytes or the modified macrophages for the treatment of musculoskeletal diseases and inducing cartilage formation are provided. Also disclosed herein are in vitro culture methods for generating the modified macrophages.

A method for modifying access of cells to extravascular spaces and regions comprising administering to a patient an enzyme that cleaves chondroitin sulfate proteoglycans is provided. It has been found that administration of an enzyme that cleaves chondroitin sulfate proteoglycans to a patient disrupts extravasation of cells from the blood stream into tissue. The present invention provides methods of reducing penetration of cells associated with inflammation into tissue of a patient. Several methods are also provided for the regulation and suppression of inflammation comprising administering enzymes that digest chondroitin sulfates. Also provided are methods of treating and preventing inflammation associated with infection, injury and disease.

Provided is a cell culture substrate for trait induction control of a macrophage, which has a pattern of unevenness on a surface to which a cell adheres, the width of the unevenness being 50 nm or more and less than 1,000 nm.

A trait induction method of undifferentiated cells is provided, including: culturing undifferentiated cells on abase material which has an uneven pattern on the surface to which the cells adhere and of which the width of the unevenness is 1 nm to 1,000 nm.

Cells such as macrophages comprising chimeric antigen receptors comprising PSMA binding FN3 domains, their conjugates, isolated nucleotides encoding the molecules, vectors, host cells, and methods of making thereof are useful in the generation of therapeutic molecules and treatment and diagnosis of diseases and disorders.