Described herein are regenerative approaches with tunable cell-cell and cell-matrix interactions to enhance the ability to regenerate multiple zones within a construct with each zone possessing a unique, optimum, level of cell-cell and cell-matrix interaction.

The present invention relates to an in vitro method for creating a viable connective tissue and/or osseous tissue obtained by tribological solicitations of a biological culture. It further relates to a viable connective tissue and/or osseous tissue susceptible to be obtained by said method as well as to the use of said method or viable connective tissue and/or osseous tissue to prepare a biological implant.

Methods and compositions are provided for the regeneration of articular cartilage by activating skeletal stem cells with a combination of (i) mechanical and (ii) biochemical stimulus. The mechanical stimulus can be an acute local injury. The biochemical stimulus can be a combination of an effective dose of a BMP2 activating agent and a VEGF inhibitor.

The present invention provides compounds of formula I:

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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.

Provided herein are a method of promoting osteogenic differentiation efficiency of a stem cell or of inducing chondrogenic differentiation of a stem cell, comprising treating the stem cell with a culture solution of chicken bone marrow-derived osteochondroprogenitor cells; a method of preventing or treating cartilage damage or a cartilage defect disease comprising administering to a subject in need thereof a composition comprising a differentiation-induced stem cell or differentiated chondrocyte made by said method as an active ingredient; and a method of preventing or treating a bone disease, cartilage damage, or a cartilage defect disease comprising administering to a subject in need thereof, a composition comprising a culture solution or culture concentrate of chicken bone marrow-derived osteochondroprogenitor cells as an active ingredient.

The present invention relates to a method for inducing differentiation, into chondrocytes, of cord blood mononuclear cell-derived induced pluripotent stem cells. In a case where a chondrogenic pellet produced by the method of the present invention is transplanted into a cartilage damage area in vivo, regeneration of cartilage can be effectively exhibited by differentiated chondrocytes. In such a case, an effective cartilage regeneration capacity can be exhibited as compared with a case where chondrocytes produced by differentiation induction with the addition of a recombinant growth factor are transplanted. Thus, the present invention can be usefully used for tissue engineering therapies.

The present invention relates to stem cells derived from villi adjacent to the chorionic plate (VCP), and a cell therapeutic agent comprising same. Stem cells derived from the tissue of VCP comprising, of the total villi, the region that is ⅓ of the distance from the area adjacent to the chorionic plate up to the villus distal part, and the basal region of the villi, according to the present invention, exhibit uniform growth characteristics, and proliferation characteristics superior to those of stem cells derived from other placental tissue, and exhibit remarkably excellent differentiation into cartilage, bone and fat, thereby being effectively usable in various tissue regeneration treatments requiring the regeneration of cartilage, bone and fat, and, particularly, in cartilage regeneration and osteoarthritis treatment.

A method for treating or repairing osteochondral damage in a subject in need thereof, including administering to the subject a cell preparation comprising pluripotent stem cells positive for SSEA-3 isolated from a body mesenchymal tissue or cultured mesenchymal cells. The pluripotent stem cells have all of the following properties: (i) CD105-positivity; (ii) low or absent telomerase activity; (iii) having ability to differentiate into any of three germ layers; (iv) absence of demonstration of neoplastic proliferation; and (v) self-renewal ability. The pluripotent stem cells are administered at 1×10.sup.3 cells to 2×10.sup.7 cells as individual.

A method of increasing the chondrogenic potential mediated by TGFβ of a mesenchymal stromal cell (MSC) or a population of mesenchymal stromal cells (MSCs), comprising the step of increasing the amount of TGFβR1, and/or decreasing the amount of TGFβR2, and/or decreasing the amount of and/or ACVRL1 of the MSC or a population of mesenchymal stromal cells (MSCs).

A method for in vitro production of cartilage tissue, which includes the steps of: i) culturing chondrocytes on an adherent culture system in a dedifferentiation culture medium that activates Wnt signaling pathway to obtain chondrocytes with a morphology of fibroblastic-like cells; ii) culturing the fibroblastic-like chondrocytes on an adherent culture system in a redifferentiation culture medium that inactivates Wnt signaling pathway to obtain chondrocytes with full capacity to resynthesize hyaline matrix; and iii) culturing the chondrocytes obtained in step ii) in a three-dimensional culture system in induction/maturation culture medium that maintain the inactivation of Wnt signaling pathway. Also, the therapeutic uses and screening methods using the cartilage tissue thus produced.