Provided herein are methods and compositions for enhancement of stem-cell based immunomodulation and promotion of tissue repair.

The present embodiments relate to an FDA-approved injectable multi-dose antigen pulsed dendritic cell (DC) vaccine. In one embodiment, the activated antigen-loaded DC vaccine comprises an initial immunizing dose and multiple “booster” doses. Also provided is a method of blocking both HER-2 and HER-3 as a treatment in causing permanent tumor senescence in HER-2 expressing breast cancers. Also provided is combination anti-estrogen therapy and anti-HER2 dendritic call vaccination for ER.sup.pos/HER2.sup.pos DCIS breast cancer patients.

Disclosed are a heterogeneous stem cell population, a preparation method therefor, and the use thereof. Specifically, disclosed is a heterogeneous stem cell population, characterized in that stem cells in the heterogeneous stem cell population express stemness genes MYC, KLF4, GMNN, SOX2 and NANOG, and in the heterogeneous stem cell population, the ratio of stem cells expressing CD146 is 1%-50%.

Disclosed herein is a T-helper cell (“T.sub.H-GM” cell) that is regulated by IL-7/STAT5 and which secrete GM-CSF/IL-3. Also disclosed are methods and compositions for modulating T.sub.H-GM function for the treatment of, e.g., inflammatory disorders. Diagnostic and prognostic methods for specifically identifying T.sub.H-GM-mediated inflammatory disorders (e.g., rheumatoid arthritis), as distinct from and/or in addition to non-T.sub.H-GM-mediated (e.g., TNF-α-mediated) inflammatory disorders, are also provided.

This invention provides methods to prepare and use immunostimulatory cells for enhancing an immune response. The invention provides a method for preparing mature dendritic cells (DCs), comprising the sequential steps of: (a) signaling isolated immature dendritic cells (iDCs) with a first signal comprising an interferon gamma receptor (IFN-γR) agonist and/or a tumor necrosis factor alpha receptor (TNF-αR) agonist to produce signaled dendritic cells; and (b) signaling said signaled dendritic cells with a second transient signal comprising an effective amount of a CD40 agonist to produce CCR7.sup.+ mature dendritic cells. Also provided by this invention are enriched populations of dendritic cells prepared by the methods of the invention. Such dendritic cells have enhanced immunostimulatory properties and increased IL-12 secretion and/or decreased IL-10 secretion. CD40 signaling can be initiated by one or more of polypeptide translated from an exogenous polynucleotide encoding CD40L (e.g., mRNA or DNA), an agonistic antibody to CD40 receptor or by CD40 ligand polypeptide. The enriched populations can be further modified by the administration of an immunogen to the DC. The DC will take up and process the immunogen on its cell surface.

The present invention provides methods of preparing a population of activated T cells by co-culturing T cells with dendritic cells loaded with a plurality of tumor antigen peptides. Also provided are methods of treating cancer in an individual using the activated T cells, pharmaceutical compositions and kits for cell-based cancer immunotherapy.

Platforms comprising at least one lymphocyte affecting molecule and at least one molecular complex that, when bound to an antigen, engages a unique clonotypic lymphocyte receptor can be used to induce and expand therapeutically useful numbers of specific lymphocyte populations. Antigen presenting platforms comprising a T cell affecting molecule and an antigen presenting complex can induce and expand antigen-specific T cells in the presence of relevant peptides, providing reproducible and economical methods for generating therapeutic numbers of such cells. Antibody inducing platforms comprising a B cell affecting molecule and a molecular complex that engages MHC-antigen complexes on a B cell surface can be used to induce and expand B cells that produce antibodies with particular specificities.

The present invention provides methods of preparing a population of activated T cells by co-culturing T cells with dendritic cells loaded with a plurality of tumor antigen peptides. Also provided are methods of treating cancer in an individual using the activated T cells, pharmaceutical compositions and kits for cell-based cancer immunotherapy.

The present disclosure is directed to systems, methods, and compositions for functional interaction of fibroblasts with one or more types of immune cells such that the interaction results in modification to the fibroblasts, the one or more types of immune cells, or both. In some embodiments, one or more certain agents are also utilized during the interaction or in lieu of one of the types of cells. In specific embodiments, cells to be used in cellular transplantation therapy are modified to have reduced immunogenicity.

Provided herein are methods for expanding populations of mesenchymal stromal cells (MSCs) comprising treating a population of MSCs derived from cord tissue with a pre-activation cytokine cocktail. Further provided herein are methods of treating immune disorders with the MSCs