The present invention provides new protease resistant polypeptides, as well as compositions and methods for treating, ameliorating or preventing conditions related to joint damage, including acute joint injury and arthritis.

The present invention relates to a medium composition for the dedifferentiation of induced pluripotency stem cells, containing a phlorotannin fraction extracted and isolated from one type of brown algae selected from the group consisting of Ecklonia cava, Dictyopteris prolifera, Dictyota coriacea, Sargassum horneri, Ishige okamurai and the like. In addition, the present invention relates to a method for preparing induced pluripotency stem cells by using the medium composition. Induced pluripotency stem cells can be safely, easily and effectively prepared by using mesenchymal stem cells by using the medium composition of the present invention, and the prepared induced pluripotency stem cells can be differentiated into various cells, and thus can be useful as a cell therapeutic agent.

A method of obtaining a neural multipotent, unipotent or somatic cell, comprising: i) providing a cell of a first type which is not a neural multipotent, unipotent or somatic cell; ii) introducing into the cell of a first type an agent capable of remodeling the chromatin and/or DNA of the cell, wherein the agent capable of remodeling the chromatin and/or DNA is a histone acetylator, an inhibitor of histone deacetylation, a DNA demethylator, and/or a chemical inhibitor of DNA methylation; iii) increasing directly or indirectly the endogenous expression of at least one neural multipotent or unipotent gene regulator in the cell of a first type, to a level at which the gene regulator is capable of driving transformation of the cell of a first type into the neural multipotent, unipotent or somatic cell, wherein the gene regulator is Msi1, Ngn2, Sox2, Ascl1, Zic1 or a combination thereof; and iv) placing or maintaining the cell in a neural cell culture medium and maintaining intracellular levels of the reprogramming agent for a sufficient period of time to allow a neural multipotent, unipotent or somatic cell to be obtained.

An in vitro human neural multipotent, unipotent, or somatic cell possessing all of the following characteristics: is derived from the reprogramming of a somatic cell, a progenitor cell or a stem cell that exhibits at least a transient increase in intracellular levels of at least one reprogramming agent; is not differentiated from a pluripotent cell; expresses one or more markers of a multipotent, unipotent or somatic cell not characteristic of a neural stem cell, neural precursor cell, neural progenitor cell, neuroblast, or neuron; is not a cancerous cell; is stable and not artificially maintained by forced gene expression and may be maintained in standard neural stem cell media or neural media; and does not exhibit uncontrolled growth, teratoma formation, and tumor formation in vivo; wherein the cell comprises at least one polypeptide or an expression vector encoding at least one polypeptide selected from the group consisting of: Musashi1 (Msi1); Ngn2; Msi1 and Ngn2; Msi1 and methyl-CpG binding domain protein 2 (MBD2); Ngn2 and MBD2; Msi1, Ngn2 and MBD2; Achaete-Scute Homolog 1 (Ascl1); Msi1, Ngn2 and Ascl1; Msi1, Ngn2, MBD2 and Ascl1; Sox2; Msi1, Ngn2 and Sox2; and Msi1, Ngn2, MBD2 and Sox2; wherein the expression vector is transiently expressed.

A method of obtaining a cardiac multipotent or unipotent cell, comprising: i) providing a cell of a first type which is not a cardiac multipotent or unipotent cell; ii) introducing into the cell of a first type an agent capable of remodeling the chromatin and/or DNA of the cell, wherein the agent capable of remodeling the chromatin and/or DNA is a histone acetylator, an inhibitor of histone deacetylation, a DNA demethylator, and/or a chemical inhibitor of DNA methylation; iii) introducing into the cell of a first type a reprogramming polypeptide and/or a polynucleotide encoding said reprogramming polypeptide, wherein the reprogramming polypeptide comprises Mesp1, Brachyury (T), Nkx2.5, and/or Tbx5; and iv) placing or maintaining the cell in a cardiac cell culture medium and maintaining intracellular levels of the reprogramming polypeptide or the polynucleotide encoding the reprogramming polypeptide for a sufficient period of time to allow a cardiac multipotent or unipotent cell to be obtained.

Provided herein are cells and methods for reprogramming iPS cells from a supercentanarian and their differentiated derivatives having differences from non-supercentenarian iPS derived cells that contribute to disease resistance and longevity. Additionally, provided herein are methods for treatment and prevention of age related diseases by administration of therapeutic sciPS derived cells or cell derived reagents. Also provided herein, are methods for identifying reagents for treatment of age related diseases using sciPS cell-based assays.

Various embodiments of the invention provide methods of treating diabetes and other glucose regulation disorders. In one embodiment, the method comprises removing L-cells from a donor, obtaining stem cells from a patient, and culturing the L-cells in the presence of the stem cells under conditions such that the stem cells differentiate into stem cell-derived L-cells (SCDLC). An amount of the SCDLC is introduced into the patient sufficient to cause a lowering of the patient's blood glucose level after ingestion of food. In another embodiment, the method comprises removing K-cells from a donor, obtaining stem cells from a patient, and culturing the K-cells in the presence of the stem cells under conditions such that the stem cells differentiate into stem cell-derived K-cells (SCDKC). An amount of the SCDKC is introduced into the patient sufficient to cause a lowering of the patient's blood glucose level after ingestion of food.

Various embodiments of the invention provide methods of treating diabetes and other glucose regulation disorders. In one embodiment, the method comprises removing L-cells from a donor, obtaining stem cells from a patient, and culturing the L-cells in the presence of the stem cells under conditions such that the stem cells differentiate into stem cell-derived L-cells (SCDLC). An amount of the SCDLC is introduced into the patient sufficient to cause a lowering of the patient's blood glucose level after ingestion of food. In another embodiment, the method comprises removing K-cells from a donor, obtaining stem cells from a patient, and culturing the K-cells in the presence of the stem cells under conditions such that the stem cells differentiate into stem cell-derived K-cells (SCDKC). An amount of the SCDKC is introduced into the patient sufficient to cause a lowering of the patient's blood glucose level after ingestion of food.

A method of treating an individual (i) having abnormal bone; or (ii) afflicted with a disease or disorder related to normal or abnormal FGF receptors or a skeletal disorder; or (iii) having dysplasic bone. The method includes administering to the individual a pharmaceutical composition comprising a therapeutically effective amount of a fibroblast growth factor 9 (FGF-9) variant comprising at least one amino acid substitution in the beta 8-beta 9 loop, wherein said FGF-9 variant incorporates one of the amino acid sequences set forth in SEQ ID NO: 11, 13, 14, 15, 16 or 17.

The present invention relates to a cellular composite comprising a 3D (three dimensional) cell growth material within which a population of chondrocytes is distributed, and which has a surface that is coated with a population of osteoblasts. The invention also relates to a method of producing said cellular composite and composites produced by the method of the invention. Further the invention relates to an in vitro model for studying healthy or diseased articular cartilage, as well as uses of the composite as an in vitro model. Finally, the invention relates to a method of screening an agent for the treatment or prevention of articular cartilage disease.