The purpose of the present invention is to efficiently produce microglia from pluripotent stem cells. Provided is a method for producing microglia from pluripotent stem cells, comprising the following steps: (a) a step of co-culturing a pluripotent stem cell together with a feeder cell for 7 days or longer, and obtaining a blood progenitor cell; (b) a step of co-culturing the blood progenitor cell obtained in step (a) together with a feeder cell in the presence of IL-3 and/or GM-CSF, and obtaining an embryonic monocyte; and (c) a step of, in the presence of M-CSF, co-culturing the embryonic monocyte obtained in step (b) together with an astrocyte, or culturing the embryonic monocyte using an astrocyte supernatant.

The invention provides culture platforms, cell media, and methods of differentiating pluriptent cells into hematopoietic cells. The invention further provides pluripotent stem cell-derived hematopoietic cells generated using the culture platforms and methods disclosed herein, which enable feed-free, monolayer culturing and in the absence of EB formation. Specifically, pluripotent stem cell-derived hematopoietic cell of this invention include, and not limited to, iHSC, definitive hemogenic endothelium, hematopoietic multipotent progenitors, T cell progenitors, NK cell progenitors, T cells, and NK cells.

There is provided inter alia according to the invention an ex vivo method of obtaining tolerogenic antigen presenting cells (APCs) that have the capability to induce tolerance in the immune system to an antigen, the method comprising (a) isolating monocytes from a sample obtained from a mammal; and (b) culturing the isolated monocytes in a cell culture to induce differentiation of the monocytes into antigen presenting cells having a tolerogenic phenotype, wherein the cell culture comprises (i) retinoic acid and TGFbeta, (ii) retinoic acid, TGFbeta and an AhR agonist or (iii) retinoic acid and an AhR agonist.

Provided are methods of in vitro maturation of spermatogonium by culturing the spermatogonium in a three-dimensional methylcellulose culture system (MCS) in a culture medium which comprises an effective concentration of a factor selected from the group consisting of granulocyte macrophages-colony stimulating factor (GM-CSF), interleukin-1 alpha (IL-1alpha), interleukin-1 beta (IL-1beta) and interleukin-6 (IL-6), under conditions capable of differentiating the spermatogonium into at least meiotic and/or postmeiotic cells, thereby in vitro maturing the spermatogonium.

Methods for using cyclin-dependent kinase (CDK) inhibitors to enhance growth and self-renewal of progenitor cells, in vitro and in vivo.

The present invention relates to novel compositions and methods to produce 3D organ equivalents of the brain (i.e. “mini-brains”). The invention also relates to methods of using human induced pluripotent stem cells, a combination of growth and other soluble factors and gyratory shaking. Cells from healthy or diseased donors or animals can be used to allow testing different genetic backgrounds. The model can be further enhanced by using genetically modified cells, adding micro-glia or their precursors or indicator cells (e.g. with reporter genes or tracers) as well as adding endothelial cells to form a blood-brain-barrier.

This disclosure is directed to, inter alia, methods and systems for preparing oligopotent and unipotent progenitor cells of defined lineages in culture from an expanded source of CD34+ cells, media for making the same, and therapeutic compounds and compositions comprising the same for treatment a variety of diseases included, but not limited to, hematologic disorders, immune diseases, cancers, and infectious diseases.

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 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.