Natural Treg (nTreg) can potentially suppress cell immune response. Consequently, these CD4+ CD25+ CD127low Foxp3+ T cells are used in adoptive therapy against autoimmune and GVH disease. One difficulty is the varying functional properties depending on the microenvironment that may cause the loss of their suppressive activity and promote TH17- induced inflammatory effects. By ex vivo transdetermination of CD31 TH0 cells, the inventors established and expanded a Foxp3 regulatory T cell population (CD31d-Treg cells) functionally committed to exert a permanent Ag-specific regulatory activity whichever the microenvironmental conditions are. By contrast to nTreg cells, CD31d-Treg cells do not express the IL1 Receptor whose activation is required for IL-17 production. Accordingly, the present invention relates to a population of CD31d-Treg cells functionally committed to exert a regulatory activity and their use for Treg-based adoptive therapy.

Described herein are the effects of continuous media perfusion on SC-Chips and the observed activation of pronounced neural tissue growth and vascular recruitment into the neural tissue channel. ALS patient chip overexpression of known neurodegenerative disease biomarkers neurogranin and neurofilament family members are also described and utilized for the invention.

The present invention relates to oligonucleotides that are capable of inducing expression of ubiquitin-protein ligase E3A (UBE3A) from the paternal allele in animal or human neurons. The oligonucleotides target the suppressor of the UBE3A paternal allele by hybridization to SNHG14 long non-coding RNA downstream of SNORD1091B. The present invention further relates to pharmaceutical compositions and methods for treatment of Angelman syndrome.

Disclosed herein is a method for enhancing antitumor T cell responses in subjects. The method involves administering to the subject in need thereof a composition comprising a demethylating agent in an amount effective to demethylate STING proteins in the tumor cells. This method is particularly useful in subjects with deficient STING expression in the tumor cells. Therefore, also disclosed is a method for treating a tumor in a subject that involves detecting in a biopsy sample from the subject reduced STING expression, reduced cGAS expression, or a combination thereof; and then administering to the subject a demethylating agent in an amount effective to demethylate STING proteins in the tumor cells. The method can further involve administering to the subject a therapeutically effective amount of a STING agonist. The method can further involve administering to the subject tumor infiltrating lymphocytes (TILs), such as HLA-matched TILs.

Compounds, compositions, and methods for generating T cells with altered phenotype are disclosed. The phenotype-altered T cells have increased persistence, prolonged survival, and increased antitumor activity and are useful for treatment of cancers.

A method of treating neurodegenerative diseases or disorders, especially Parkinson's disease and a method of inducing neural stem cells from peripheral blood mononuclear cells. The induced neural stem cells can express neural stem cell-related genes and differentiate into neurons, astrocytes and oligodendrocytes. The dopaminergic precursors derived from the induced neural stem cells are transplanted into the striatum of the PD mouse models without any sign of tumorigenesis, thereby improving the behaviors of the PD mouse models and slowing down the progression of Parkinson's disease.

This application describes liver stem cells (LSC), and differentiated hepatocytes, cholangiocytes, and 3D cellular structures derived therefrom. Methods for producing LSC and mature, differentiated hepatocytes and cholangiocytes in culture are provided. Also provided are cell culture systems and cell culture media for producing a homogenous population of liver stem cells that remain in an undifferentiated state over multiple passages in culture. The LSC and methods are useful for producing homogenous populations of hepatocytes and cholangiocytes for downstream applications. The LSC can be transplanted into subjects to treat liver diseases.

Disclosed are means, methods, and compositions of matter useful for treatment of neuroinflammation, autoimmunity, transplant rejection, or graft versus host disease (GVHD) comprising exposing autologous immune cells to allogeneic amniotic fluid derived stem cells. In one embodiment peripheral blood mononuclear cells are cultured in the presence of amniotic fluid stem cells in the presence of interleukin-2 for a period of time sufficient to endow tolerogenic properties. Said tolerogenic properties include ability to suppress adaptive or innate immune responses. In another embodiment the invention provides methods of generating antigen specific immune regulatory cells by culture of lymphocytes together with amniotic fluid stem cells in the presence of antigen to which specific immune regulation is desired.

Maturation signals provided via cyclic adenosine monophosphate (cAMP)/Exchange proteins activated by cAMP (Epac) signaling during in vitro generation of blood cells from reprogrammed cells or pluripotent stem cells achieve superior function of hematopoietic cells differentiated from stem cells. The cAMP/Epac signaling enables an increased efficiency of production of precursor to blood and to blood cells. These generated blood cells can be utilized for therapeutics, treatments, disease prevention, drug discovery, personalized medicine, regenerative medicine, cell and tissue generation, universal donor banks and related methods and compositions.

Provided herein are hepatocyte-like cells with enhanced in vitro ureagenesis capability and methods for producing and using such cells. The subject hepatocyte-like cells are produced by differentiating a source cell into a hepatocyte-like cell in the presence of one or more ureagenesis enhancer. The subject hepatocyte-like cells provided are useful for the treatment of liver disorders, particularly those where hepatocyte ureagenesis function is impaired.