The invention disclosed herein generally relates to methods and systems for improving physiological growth of cultured tissues. In particular, the invention disclosed herein relates to methods and systems for promoting maintenance of cultured intestinal organoids (e.g., derived from pluripotent stem cells or from primary sources such as biopsy tissue).

The present invention relates to the field of stem cell biology, in particular the linage specific differentiation of pluripotent or multipotent stem cells, which can include, but is not limited to, human embryonic stem cells (hESC), human induced pluripotent stem cells (hiPSC), somatic stem cells, cancer stem cells, or any other cell capable of lineage specific differentiation. Specifically described are methods to direct the lineage specific differentiation of hESC and/or hiPSC to nociceptors (i.e. nociceptor cells) using novel culture conditions. The nociceptors made using the methods of the present invention are further contemplated for various uses including, but limited to, use in in vitro drug discovery assays, pain research, and as a therapeutic to reverse disease of, or damage to, the peripheral nervous system (PNS). Further, compositions and methods are provided for producing melanocytes from human pluripotent stem cells for use in disease modeling.

The present invention provides a method for producing parasympathetic neurons from neural crest cells or autonomic neural progenitor cells derived therefrom, comprising a step of culturing the neural crest cells or autonomic neural progenitor cells derived therefrom in the presence of a cAMP production promoter, a BDNF signaling pathway activator, a GDNF signaling pathway activator, an NGF signaling pathway activator, an NT-3 signaling pathway activator, vitamin C, a protein kinase C activator, and a retinoic acid receptor agonist.

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.

Human pluripotent stem cells are differentiated in vitro into forebrain subdomain structures, which are then fused to generate an integrated system for use in analysis, screening programs, and the like.

The present invention is drawn, in part, to biocompatible compositions comprising a biocompatible polymer matrix and conditioned cell medium comprising i) a cell culture medium and ii) one or more agents synthesized by and secreted from one or more cells cultured in the cell culture medium, as well as therapeutic uses thereof, particularly in modulating bone and/or gum tissue growth.

Cell culture media, preservative media or cryopreservation media include a low dose of one or more cytokines, e.g. interleukin-2 (IL-2).

In certain aspects, the present disclosure provides methods and materials for detection and characterization of retinal ganglion cells in a sample. In accordance with certain embodiments, the present disclosure provides systems and methods for detection of disease or diseased states related to retinal ganglion cells. In some forms the disclosure provides for a method for diagnosing a disease or diseased state related to retinal ganglion cells in a patient, the method comprising the step of detecting in a body fluid of the patient one or more markers associated with the disease or diseased state.

Organs-on-chips are microfluidic devices for culturing living cells in micrometer sized chambers in order to model physiological functions of tissues and organs. Engineered patterning and continuous fluid flow in these devices has allowed culturing of intestinal cells bearing physiologically relevant features and sustained exposure to bacteria while maintaining cellular viability, thereby allowing study of inflammatory bowl diseases. However, existing intestinal cells do not possess all physiologically relevant subtypes, do not possess the repertoire of genetic variations, or allow for study of other important cellular actors such as immune cells. Use of iPSC-derived epithelium, including IBD patient-specific cells, allows for superior disease modeling by capturing the multi-faceted nature of the disease.

The invention relates to improved culture methods for expanding epithelial stem cells and obtaining organoids, to culture media involved in said methods, and to uses of said organoids.