The present invention provides an isolated population of chondrocyte precursor cells wherein 1% or less of the cells express Oct4, Nanog and/or TRA-1-60, 7% or less of the cells express no collagen II, collagen X, CD105 or Stro-1 and 85% or more of the cells express CBFA1, methods for preparing such cells and uses of chondrocyte cells derived from said precursor cells.

Methods of generating functional human brown adipocytes, comprising exposing human stem cells, progenitor cells, or white adipocytes to culture with an differentiation cocktail that comprises one or more browning agents (e.g., one or more macromolecular crowders), and optionally one or more adipogenic agents, are described, as are populations of human brown adipocytes generated by the methods, and uses for the populations. Methods of generating functional human brown adipocytes in an individual, such as by administering a pharmaceutical composition comprising an differentiation cocktail, are also described.

The invention provides a method of producing a connective tissue graft suitable for correcting a connective tissue defect, comprising determining the size and shape of a tissue defect, obtaining a fat tissue from a patient modelled to fit the size and shape of the tissue defect, contacting the fat tissue with one or more connective tissue specific growth or differentiation factors; and kits for such a method.

The invention provides a quiescent stem cell having the capacity to differentiate into ectoderm, mesoderm and endoderm, and which does not express cell surface markers including MHC class I, MHC class II, CD44, CD45, CD13, CD34, CD49c, CD73, CD105 and CD90. The invention further provides a proliferative stem cell, which expresses genes including Oct-4, Nanog, Sox2, GDF3, P16INK4, BMI, Notch, HDAC4, TERT, Rex-1 and TWIST but does not express cell surface markers including MHC class I, MHC class II, CD44, CD45, CD13, CD34, CD49c, CD73, CD105 and CD90. The cells of the invention can be isolated from adult mammals, have embryonic cell characteristics, and can form embryoid bodies. Methods for obtaining the stem cells, as well as methods of treating diseases and the differentiated stem cells, are also provided.

The presently disclosed subject matter provides hydrogel precursor compositions (e.g., solutions) for forming three-dimensional hydrogels that support growth of physiologically relevant tissue when at least one cell is cultured in the three-dimensional hydrogel, kits comprising the hydrogel precursor composition, three-dimensional hydrogels, methods of forming the three-dimensional hydrogels, methods of growing the physiologically relevant tissue using the three-dimensional hydrogels, physiologically relevant tissue grown in the three-dimensional hydrogels, methods of producing hormone-responsive tissue (e.g., milk-producing mammary tissue and related methods of producing milk), methods of screening for candidate agents useful for modulating hormonal responses (e.g., modulating milk production), method of screening for candidate therapeutic agents using the physiologically relevant tissue grown in the three-dimensional hydrogels (e.g., personalized cancer treatments), and related methods of treatment (e.g., administering agents identified using the methods herein, transplanting physiologically relevant tissue produced using the methods, etc.).

The present invention relates to a method for the production of differentiated respiratory epithelial cells comprising: (a) providing a cell population comprising or consisting of precursor cells of respiratory epithelial cells; (b) culturing the cell population of (a) in culture medium to which keratinocyte growth factor has been added; wherein the cultured cell population is supplemented with a glucocorticoid, a cAMP analog and a cAMP elevating agent and wherein said supplementation is either simultaneously with the addition of keratinocyte growth factor in step (b) or prior or subsequently to the addition of keratinocyte growth factor in step (b), thereby differentiating said precursor cells into respiratory epithelial cells. The present invention further relates to the cell(s) obtained by the method of the invention for use in treating or preventing a respiratory disease and to a method for identifying a compound having an pharmacological, cytotoxic, proliferative, transforming or differentiating effect on the differentiated respiratory epithelial cells obtained by the method of the invention.

A serum-free complete medium for inducing differentiation of a mesenchymal stem cell to a corneal epithelial cell in the field of differentiation induction of stem cells, prepared by the following method: uniformly mixing the serum-free complete medium, containing 5-10 μmol of resveratrol, 2-4 μmol of icariin, 1-3 nmol of aspirin, 1-3 nmol of parathyroid hormone, 5-10 nmol of hydrocortisone, 1-3 mg of rapamycin, 2-10 μg of testosterone, 2-10 μg of EPO, 2-10 μg of LIF and the balance of a corneal epithelial cell serum-free medium in per 1 L; and then performing sterilization by filtration. The disclosure uses resveratrol and icariin in combination with aspirin, parathyroid hormone, hydrocortisone, rapamycin, testosterone and growth factors to cooperatively induce directional differentiation, uses nontoxic induction components, is high in induction efficiency and short in induction time, and achieves high induced corneal epithelial cell activity, no cell transplantation rejection, no ethical problem and high safety.

The present invention provides a method starting from cells derived from a mammalian endodermal tissue or organ (except for the liver) to produce stein/progenitor cells thereof, which comprises bringing the cells derived from the endodermal tissue or organ into contact in vitro with a TGFβ-receptor inhibitor.

The invention provides pharmaceutical compositions comprising human immature dental pulp stem cells (hIDPSCs) wherein the hIDPSCs express CD44 and CD13. The invention also provides methods of treating a neurological disease or condition comprising systemically administering to a subject a pharmaceutical composition comprising hIDPSCs wherein the hIDPSCs express CD44 and CD13. For example, for treating neurological diseases or conditions including supporting the neuro-protective mechanism in subjects diagnosed with early HD or repairing lost DA neurons in subjects diagnosed with PD.

This application relates to non-human primate (NHP) induced pluripotent stem cell (IPSC)-derived hepatocytes, for example, Cynomolgus monkey (Macaca fascicularis) induced pluripotent stem cell-derived hepatocytes, and methods of producing the same. Moreover, this application relates to methods of using NHP IPSC-derived hepatocytes for drug screening, drug safety assessment and in models of infection.