The invention provides tissue culture system for primary cells (e.g. normal mammalian primary epithelial progenitors). This system includes: a) a serum-free, chemically defined cell culture media; and, b) methods for isolation and in vitro long-term propagation of primary cells (e.g. primary epithelial cells). Primary cells so isolated and cultured can be kept undifferentiated and proliferate for many weeks (>15 weeks) or population doubling (>35 PD) without senescence, or any detectable genetic alterations. Upon changing media/culture conditions, these cells can be induced to differentiate.

The invention also provides methods to transform normal primary cells so cultured into cancer stem cells. The genetically defined cancer stem cell tumor model mimics the behavior of the disease closely, e.g., the cells are invasive, hormone responsive and metastatic when injected into mice. The tumor cells express genes that are specific to cancer stem cells identified in patient samples.

We report human cerebellar organoids which recapitulate the major milestones of cerebellar development including generating bona fide Purkinje cells, as well as methods of making and using these human cerebellar organoids such as uses in drug target identification and drug screening. In various embodiments, we report a human organoid model (human cerebellar organoids [hCerOs]) capable of developing the complex cellular diversity of the fetal cerebellum, including a human-specific rhombic lip progenitor population that have never been generated in vitro prior to our study. 2-month-old hCerOs form distinct cytoarchitectural features, including laminar organized layering, and create functional connections between inhibitory and excitatory neurons that display coordinated network activity. Long-term culture of hCerOs allows healthy survival and maturation of Purkinje cells that display molecular and electrophysiological hallmarks of their in vivo counterparts, addressing a long-standing challenge in the field.

The invention relates to a culture medium comprising an inhibitor of the BMP signaling pathway; and an inhibitor of the TGF/activin/nodal signaling pathway and to a method for obtaining a population of neural precursors using said culture medium.

The present disclosure describes compositions for preparing a myofiber or myotube from a skeletal muscle stem cell or progenitor cell comprising a carnitine and/or a derivative thereof, a fatty acid a steroid and combinations thereof. Preferred embodiment comprises of 0.1 mM L-carnitine, 0.2 mM 9-cis-linoleic acid and 10 mM dihydrotestosterone. Also disclosed is a composition for inducing expansion of skeletal muscle stem cells or progenitor cells comprising a fibroblast growth factor agonist, a Notch signalling agonist, a nucleic acid, and combinations thereof. Preferred embodiment comprises 20 ng/ml basic fibroblast growth factor (bFGF), 50 g/ml Delta-like ligand 1 (DLL1), 10 mM hypoxanthine and 1.6 mM thymidine.

The present invention relates to a method for increasing the galactose content of a recombinant protein produced in mammalian cells, wherein during the cultivation of said cells the pH of the cell culture is changed and a composition comprising nucleosides, transition metal salts and/or sugars is fed.

The present invention is directed towards methods of culturing non-keratinocyte epithelial cells, with the methods comprising culturing non-keratinocyte epithelial cells in the presence of feeder cells and a calcium-containing medium while inhibiting the activity of Rho kinase (ROCK) in the feeder cell, the non-keratinocyte epithelial cells or both during culturing.

The invention relates to immuno-oncology mesodermal progenitor (ioMP) cells and their use in therapy.

A method for treating an oral condition of a subject by grafting cultured tissue constructs to the oral tissue. The cultured tissue constructs comprise cultured cells and endogenously produced extracellular matrix components without the requirement of exogenous matrix components or network support or scaffold members. Some tissue constructs of the invention are comprised of multiple cell layers or more than one cell type. The tissue constructs of the invention have morphological features and functions similar to tissues their cells are derived and their strength makes them easily handleable. Preferred cultured tissue constructs of the invention comprise cells derived from human tissue.

An object of the present invention is to provide an animal cell culture method which is high in protein productivity.

Provided is a method for culturing animal cells in a culture medium, wherein the culture medium comprises a nucleic acid component(s) (deoxyuridine, thymidine, and/or deoxycytidine, or a salt(s) thereof). Also provided is a method for producing a protein, the method comprising the step of culturing animal cells expressing the protein in a culture medium, wherein the culture medium comprises a nucleic acid component(s).

The present invention relates to methods for generating mammalian multilineage-potential cells, including mesenchymal stem cells, comprising contacting mammalian somatic cells exhibiting a mature phenotype with PDGF-AB or functional derivative, fragment or mimetic thereof and Azacitidine or functional derivative or analog thereof for a time and under conditions sufficient to induce the transition of the somatic cells to cells exhibiting multilineage differentiative potential. Also provided are uses of said multilineage-potential cells, such as in promoting tissue repair and regeneration.