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.

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.

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.

Methods of inducing a polarization of macrophages. The method includes obtaining a blood fraction, fractionating the blood fraction to produce a blood fraction, and contacting the blood fraction with a source of macrophages. A blood fraction including platelet-poor plasma polarizes the source of macrophages into M1 macrophages. A blood faction including a protein solution polarizes the source of macrophages into M2 macrophages.

The present invention is directed to indirect ultrasonic cavitation-derived perivascular cells, to methods of use of a perivascular cell composition, to a method of processing a tissue and to an apparatus for the processing of a tissue. The methods include the mechanic indirect ultrasonication of a cellular non-structural tissue, and produce a perivascular fraction which includes perivascular cells. The methods of use are directed to the treatment of a variety of diseases and disorders and to the improvement of a tissue in a subject. The apparatus is provided for the processing of cellular non-structural tissue.

A system and a method are disclosed for obtaining a plasma composition enriched with bioactive molecules such as growth factors and cytokines and depleted in contaminants such as viruses.

Alveolar-like macrophages and a method for generating alveolar-like macrophages from hemangioblasts is provided. The method comprises the steps of: i) culturing the hemangioblasts in a hematopoietic-inducing medium comprising vascular endothelial growth factor (VEGF), stem cell factor (SCF) and interleukin-3 (IL-3) for a sufficient period of time to generate macrophages, and ii) culturing the macrophages in an alveolar macrophage-inducing medium comprising granulocyte macrophage colony stimulating factor (GM-CSF), and optionally macrophage colony stimulating factor (M-CSF), under suitable conditions and for a sufficient period of time to yield alveolar-like macrophages.

The present invention includes methods and compositions for treating cancer, whether a solid tumor or a hematologic malignancy. By expressing a chimeric antigen receptor in a monocyte, macrophage or dendritic cell, the modified cell is recruited to the tumor microenvironment where it acts as a potent immune effector by infiltrating the tumor and killing the target cells. One aspect includes a modified cell and pharmaceutical compositions comprising the modified cell for adoptive cell therapy and treating a disease or condition associated with immunosuppression.