Embodiments of the disclosure concern methods and compositions related to treatment of diabetes and/or related conditions using cell therapy. In specific embodiments, cells that lacked the ability to produce insulin are exposed to one or more particular agents that render the cells to have the ability to produce insulin, and these cells are provided to an individual in need thereof. In a specific embodiment, the agent(s) are Wnt5a, FGF7, WNT3a, HGF, THBS2, IGF1, PDPN, LIF, endocan, SERPINF1, EGF, or a combination thereof.

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.

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 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.

Compositions and methods of transplanting cells by grafting strategies into solid organs (especially internal organs) are provided. These methods and compositions can be used to repair diseased organs or to establish models of disease states in experimental hosts. The method involves attachment onto the surface of a tissue or organ, a patch graft, containing the donor cells. The donor cells may be a mixture of stem cells/progenitors with supporting early lineage stage mesenchymal cells. The patch graft promotes migration of the donor cells into the host organ and supports the successful integration of donor cells with host cells to repair the diseased organ.

Compositions and methods of transplanting cells by grafting strategies into solid organs (especially internal organs) are provided. These methods and compositions can be used to repair diseased organs or to establish models of disease states in experimental hosts. The method involves attachment onto the surface of a tissue or organ, a patch graft, a bandaid-like covering, containing epithelial cells with supporting early lineage stage mesenchymal cells. The cells are incorporated into soft gel-forming biomaterials prepared under serum-free, defined conditions comprised of nutrients, lipids, vitamins, and regulatory signals that collectively support stemness of the donor cells. The graft is covered with a biodegradable, biocompatible, bioresorbable backing used to affix the graft to the target site. The cells in the graft migrate into and throughout the tissue such that within a couple of weeks they are uniformly dispersed within the recipient (host) tissue. The mechanisms by which engraftment and integration of donor cells into the organ or tissue involve multiple membrane-associated and secreted forms of MMPs.

Invention embodiments described herein include methods and devices for stimulating mesenchymal stem cells in a stem cell source to differentiate into osteoblasts capable of forming bone. Devices and methods described include exposing a stem cell source, such as bone marrow aspirate, adipose tissue and/or purified allogenic stem cells, to an active agent, in a manner effective to form activated stem cells.

The purpose of the present invention is to provide immortalized stem cells, which produce a growth factor capable of regenerating various kinds of tissues that have been damaged by a variety of causes, and a method for producing the aforesaid immortalized stem cells. Another purpose is to provide a medicinal composition and a medicinal preparation for restoring damaged tissues, and a method for the percutaneous absorption of a culture supernatant. Provided are immortalized stem cells that are obtained by isolating stem cells selected from the group consisting of mammalian mesenchymal cells, an embryo at the early stage of the development and somatic cells, first culturing the cells to give first stage culture cells, transferring four kinds of genes into the first stage culture cells to give transgenic cells, and selecting the desired immortalized stem cells from among the transgenic cells using the expression of STRO-1 as an index.

The present invention provides compounds of formula I:

##STR00001##

or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, wherein the variables are as defined herein. The present invention further provides pharmaceutical compositions comprising such compounds, and methods of using such compounds for treatment of joint damage or joint injury in a mammal, and for inducing differentiation of mesenchymal stem cells into chondrocytes.