Methods of culturing embryonic stem cells, induced pluripotent stem cells and/or differentiated cells in culture medium comprising activin are described. In one aspect, the disclosure features a pluripotent human stem cell, wherein the stem cell comprises: (i) a genomic edit that results in loss of function of Cytokine Inducible SH2 Containing Protein (CISH) and (ii) a genomic edit that results in a loss of function of an agonist of the TGF beta signaling pathway, or a genomic edit that results in a loss of function of adenosine Ata receptor.

Disclosed herein are compositions and methods that involve using compositions containing one or more of ETV2, FOXC2, FLI1 and a miR-200b inhibitor for directly reprogramming somatic cells into induced vasculogenic cells both in vitro and in vivo. These compositions and methods are useful for a variety of purposes, including the development of pro-angiogenic therapies.

Compositions and methods are provided for production of cells useful in regenerative therapies.

There is provided a mutant KLF protein that can induce reprogramming of a somatic cell at a higher efficiency than a KLF protein having a natural amino acid sequence. There is also provided a method for efficiently producing an iPS cell by using the mutant KLF protein. There is provided a mutant KLF protein having an amino acid substitution, or a peptide fragment thereof containing the amino acid substitution.

Methods for treating a cell, tissue, or organ and for treating an age-related disease or condition are provided, where the cell, tissue or organ is contacted with a synthetic, persistent RNA vector comprising one or more heterologous polynucleotide sequences, each of the one or more heterologous polynucleotide sequences encoding for a reprogramming factor. Contacting achieves expression of the one or more reprogramming factors in the cell, tissue, or organ to treat the age-related disease or condition. In an embodiment, the method is used to obtain a rejuvenated cell, tissue, or organ with retention of cellular identity.

The present invention provides for identification and use of small molecules to induce pluripotency in mammalian cells as well as other methods of inducing pluripotency.

The present invention provides a method with which it is possible to directly induce nervous system cells efficiently and in a short amount of time. Because the method is easy to scale up and is not affected by the characteristics or background of the somatic cells used as material, the method enables the stable supply of nervous system cells. The nervous system cells obtained by the method are useful in various fields of research and healthcare.

The present invention relates to a method of converting human fibroblasts into neural stem cells, and more particularly, to a method of directly converting human fibroblasts into neural stem cells using only a combination of small-molecule compounds without any introduction of a foreign gene, and to the use of the neural stem cells. The method of directly converting human fibroblasts into neural stem cells using only small-molecule compounds without any introduction of a foreign gene makes it possible to obtain genetically stable neural stem cells in an amount sufficient for use in cell therapy by deriving them from human fibroblasts. The neural stem cells obtained according to the method of the present invention can differentiate into functional neural cells and are not tumorigenic. Thus, these neural stem cells are useful as cellular therapeutic agents for treatment of brain diseases.

Over the course of an aging process fibroblasts lose contractility, leading to reduced connective tissue stiffness. A promising therapeutic avenue for functional rejuvenation of connective tissue is reprogrammed fibroblast replacements with a laterally confined growth of fibroblasts on micro-patterned substrates that induces stem cell-like spheroids. The partially reprogrammed spheroids are embedded in collagen-I matrices of varying densities, mimicking different 3D tissue constraints. The spheroids regain their fibroblastic properties and sprout to form 3D connective tissue networks. The differentiated fibroblasts exhibit reduced DNA damage, enhanced cytoskeletal gene expression and acto-myosin contractility. The rejuvenated fibroblasts show increased matrix protein (fibronectin and laminin) deposition and collagen remodeling compared to the parental fibroblast tissue network. The partially reprogrammed cells have comparatively open chromatin compaction states and may be more poised to redifferentiation into contractile fibroblasts in 3D-collagen matrix. Collectively, the results highlight efficient fibroblast rejuvenation, with important implications in regenerative medicine.

The present invention provides a method of treating a disorder using a fibromodulin (FMOD) reprogrammed (FReP) cell. The method comprises administering locally to a human being the FReP cell to a site in need thereof of the human being.