Compositions comprising a condensed mesenchymal cell body and a hydrogel are provided. The compositions may further include drugs or growth factors. The condensed mesenchymal cell body may include a connective tissue cell, or even a progenitor cell capable of producing connective tissue extracellular matrices such collagen and glycosaminoglycan. Also provided are methods of treating connective tissue defects, cartilage injury, and cartilage degradation.

The present disclosure aims to provide a manufacturing method of a cell structure. The manufacturing method comprises a preparation step of preparing, on a culturing surface of a cell culture container, a first coated region coated with a temperature-responsive polymer and/or a temperature-responsive polymer composition, and a plurality of second coated regions located at an edge of the first coated region and coated with a cell adhesive substance; and a seeding and culturing step of seeding cells in the first coated region and the second coated regions and culturing the cells to produce a cell structure.

The present invention provides methods for obtaining mesenchymal stem cell (MSC)-derived cells of chondro-osteoblastic lineage from MSC. The invention also relates to a population of MSC-derived cells of chondro-osteoblastic lineage obtained by the methods, a pharmaceutical formulation comprising the population of MSC-derived cells of chondro-osteoblastic lineage, and their use in the treatment of a subject in need of transplantation of cells of chondro-osteoblastic lineage.

The present invention refers to a method of manufacturing an implantable construct comprising chondrogenically differentiated cells and one or more polycaprolactone (PCL) microcarriers, an implantable construct produced using said method, and uses of the implantable construct. The present invention also refers to a method of manufacturing an implantable construct comprising mesenchymal stromal cells and one or more polycaprolactone (PCL) microcarriers, an implantable construct produced using said method, and uses of the implantable construct. The present invention further refers to a method of treating a disease or disorder associated with cartilage and/or bone defect, the method comprises administering one or more cell-free polycaprolactone (PCL) microcarriers in a patient suffering from the disease or disorder.

Provided is an isolated population of human pluripotent stem cells comprising at least 50% human pluripotent stem cells characterized by an OCT4+/TRA1-60−/TRA1-81−/SSEA1+/SSEA4− expression signature, and novel methods of generating and maintaining same in a pluripotent, undifferentiated state a suspension culture devoid of cell clumps. Also provided are novel culture media, cell cultures and methods for culturing pluripotent stem cells in a suspension culture or a two-dimensional culture system while maintaining the cells in a proliferative, pluripotent and undifferentiated state. The novel culture media comprise interleukin 11 (IL11) and Ciliary Neurotrophic Factor (CNTF); bFGF at a concentration of at least 50 ng/ml and an IL6RIL6 chimera; or an animal contaminant-free serum replacement and an IL6RIL6 chimera. Also provided are methods for generating lineage-specific cells from the pluripotent stem cells.

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 invention relates to a method for producing cartilage from pluripotent stem cells (PSCs), the method comprising providing chondrocytes by: 1) providing pluripotent stem cells (PSCs); 2) inducing differentiation of the PSCs into a primitive streak/mesendoderm by culturing the PSCs in hypoxic conditions, in a (mesendodermic) culture media comprising: i) a Wingless/Integrated (WNT) family member, ii) an Activin family member, and iii) a Fibroblast Growth Factor (FGF) family member; 3) inducing differentiation of the primitive streak/mesendoderm into a mesoderm by culturing the primitive streak/mesendoderm in hypoxic conditions, in a (mesodermic) culture media comprising: i) a FGF family member, ii) a bone morphogenetic protein (BMP) family member, iii) Follistatin, and iv) a Neurotrophin (NT); and 4) inducing differentiation of the mesoderm into chondrocytes by culturing the mesoderm in hypoxic conditions, in a (chondroinductive) culture media comprising: i) a FGF family member, ii) a BMP family member, iii) a Neurotrophin, and iv) a Growth/Differentiation Factor (GDF) family member; and forming a pellet of the chondrocytes and culturing the pellet of the chondrocytes in a culture media under hypoxic conditions to produce the cartilage. The invention further relates to methods of chondrocyte production, synthetically produced cartilage, and use in therapy.

The present application is directed to a method of treating osteoarthritis, which includes obtaining a member of a transforming growth factor superfamily of proteins; obtaining a population of cultured mammalian cells that may contain vector encoding a gene, or a population of cultured connective tissue cells that do not contain any vector encoding a gene; and then transferring the protein and the connective tissue cells into an arthritic joint space of a mammalian host, such that the activity of the combination within the joint space results in regenerating connective tissue.

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.

Provided is reproducible means that enables the production of an active nucleus pulposus cell phenotype from desired cells such as terminally differentiated cells or pluripotent or multipotent stem cells. Provided is a differentiation inducer containing an effective amount of a gene of at least two transcription factors selected from the group consisting of Brachyury (T), SRY-box6 (SOX6), C and Forkhead Box Q1 (FOXQ1), or homologs thereof (nucleus pulposus cell master regulator transcription factor), or a product thereof.