Provided herein is a differentiation agent that consist essentially of SOX9 for the production of oligodendrocyte progenitor cells (OPCs) from pluripotent stem cells (PSCs). Also provided herein are methods of producing the PSCs and methods of using the PSCs to produce OPCs and oligodendrocytes.

Disclosed are means, methods and compositions of matter useful for inhibiting, in an antigen-specific manner, immunity towards an autoantigen or alloantigen. In one embodiment of the invention, regenerative cells are cultured ex vivo together with immune cells from a mammal suffering from an autoimmune condition. Autoantigens or alloantigens are added in the culture of regenerative cells and cells from an autoimmune disease suffering individual in a manner so that said regenerative cells can endow onto said immune cells of said patient suffering from autoimmunity a state of antigen specific infectious tolerance. In one embodiment, said infectious tolerance involves T regulatory cells inducing conversion of dendritic cells to tolerogeneic dendritic cells, and furthermore in other embodiments administration of tolerogenic dendritic cells induces T regulatory cells.

The present disclosure relates to the in vitro differentiation of memory B cells to plasmablasts or plasma cells and genetic modification of these cells to express a protein of interest, such as a specific antibody or other protein therapeutic.

A method of differentiating pluripotent stem cells into hemangioblasts comprising incubating the pluripotent stem cells in a first serum-free differentiation medium comprising bone morphogenetic protein 4 (BMP4), vascular endothelial growth factor (VEGF) and stem cell factor (SCF) to induce differentiation of the pluripotent stem cells into hemangioblasts or hemangioblast-containing embryoid bodies is provided. The hemangioblasts or embryoid bodies may be cultured in a second differentiation medium comprising at el least granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage colony stimulating factor (M-CSF) and interleukin-3 (IL-3) for a period of time sufficient to generate alveolar-like macrophages.

The current invention concerns an isolated mesenchymal stem cell wherein said cell is measuredpositive for mesenchymal markers CD29, CD44 and CD90; and negative for MHC class II molecules,whereinsaid cell secretes immunomodulatory prostaglandin E2 cytokine when present in an inflammatory environment or condition. The current invention also concerns a cell composition comprising said cells and the use thereof in the treatment of immune-related diseases and inflammatory conditions.

A pharmaceutical composition includes a silicified cell or fraction thereof, a cationic layer disposed on at least a portion of the surface of the silicified cell or fraction thereof, and an immunomodulatory moiety bound to at least a portion of the cationic layer. Alternatively, the pharmaceutical composition includes a silicified cell or fraction thereof, a cationic layer disposed on at least a portion of the surface of the silicified cell or fraction thereof, an anionic layer disposed on at least a portion of the cationic layer, and an immunomodulatory moiety bound to at least a portion of the anionic layer.

A methodology to obtain large numbers of allospecific human Tr1 lymphocytes in vitro differentiated with phenotype and suppressive function stability in presence of proinflammatory cytokines, by using donor tolerogenic dendritic cells (DC10) derived from donor monocytes and from a not related receptor (allogeneic) naîve T cells cocultures. The obtained cells with the present methodology are characterized by the expression of a Tr1 regulatory phenotype (CD4+, CD49b+, LAG-3+), being high IL-10 producers, and also they express additional co-inhibitory molecules as PD1, TIM-3, CD39, CTLA-4 y TIGIT. Moreover, the cellular product obtained by this methodology is able to maintain a stable phenotype and suppressive function in presence of proinflammatory cytokines (IL-1β, IL-6, IFN-γ y TNF-α). The numbers, purity, and stability of the Tr1 obtained by this methodology, make them great candidates for their use as therapeutic tools in transplantation.

The present disclosure provides a population of poly-donor CD4.sup.IL-10 cells generated by genetically modifying CD4.sup.+ T cells from at least three different T cell donors. Further provided are methods of generating the poly-donor CD4.sup.IL-10 cells and methods of using the poly-donor CD4.sup.IL-10 cells for immune tolerization, treating GvHD, cell and organ transplantation, cancer, and other immune disorders.

The present disclosure provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to an immunoresponsive cell comprising an antigen-recognizing receptor (e.g., a chimeric antigen receptor (CAR) or a T cell receptor (TCR)), and expressing increased level of IL-36. In certain embodiments, the engineered immunoresponsive cells are antigen-directed and have enhanced immune-activating properties.

A nucleic acid molecule comprising a nucleotide sequence encoding a homodimeric IL-10 linked to a transmembrane-intracellular stretch, optionally through a flexible hinge, is provided as well as a mammalian regulatory T cell (Treg) comprising and expressing the nucleic acid molecule and uses thereof.