A composition according to an embodiment includes a first population of transformed mammalian cells with a transforming growth factor beta (TGF-β), the first population having a TGF-β expression level of 0.65 ng/10.sup.5 cells/24 hours or more, and a second population of mammalian cells which are not transformed with the transforming growth factor beta, the second population having an expression level of a thrombospondin 1 (TSP-1) expression level of 31 ng/10.sup.5 cells/24 hours or more.

Disclosed is a method of constructing a cell sheet using only cells without a support. More particularly, a method of manufacturing a multi-layered cell sheet without a separate lamination step and a cell sheet manufactured by the method are disclosed.

The present invention pertains to a method for creating reprogramed cells from somatic cells without gene introduction. The method includes a step (a) for culturing somatic cells in a medium containing a histone deacetylase inhibitor, and a step (b) for culturing the cells cultured in step (a) in a medium containing an OCT3/4 transcription stimulating factor to create reprogrammed cells.

Disclosed herein are compositions, devices, methods, processes, and systems for culturing of large quantities of mammalian cells in suspension culture. Also disclosed are unique and surprising cell populations derived from the disclosed methods, processes, and systems. In many embodiments, the cells are cultured in suspension in liquid culture media that is agitated to maintain the cells in suspension, and agitation increases to maintain cells in suspension while growing and dividing to create cell spheres. The disclosed devices, methods, processes, and systems are useful in tailoring characteristics of the resulting cells based on characteristics of donor subject/initial cells. The disclosed cell populations are useful in treating subjects with cell based therapies in need thereof for various diseases and conditions.

The present invention provides a new method related to regenerative medicine for the treatment of cartilage disorders, osteoarthritis and cartilage injury in particular. More particularly, it relates to an FGF-18 compound for use in tissue engineering and graft procedures, such as osteochondral or cartilage transplantation or autologous chondrocyte implantation (ACI).

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.

The present invention provides a limb bud mesenchymal cell population, which is derived from mammalian lateral plate mesoderm cells, and is PRRX1 protein-positive.

Multiple component grafts are provided for treatment of tissue defects and comprise two or more components, each of which is a tissue-derived matrix and at least two of which are derived from different types of tissue. For example, a first component may be a matrix derived from cartilage tissue such as cartilage fibers with or without viable cells, cartilage particles with or without viable cells, or combinations of any two or more such cartilage-derived matrices. A second component may be a matrix derived from bone tissue such as mineralized or demineralized cortical bone fibers, viable cancellous bone matrix (e.g., cryopreserved or lyophilized chips, particulates, powder, sheets, putty, flowable fluid, etc.), demineralized or demineralized cancellous bone matrix (chips, particulates, powder, sheets, putty, flowable fluid, etc.), or combinations of any two or more of such bone-derived matrices. Also provided are methods for making and using such multiple component grafts.

Methods of bioprinting a bio-ink construct on an internal tissue defect or a chondral defect during a minimally invasive surgery on an individual in need thereof are provided, comprising: visualizing the defect; positioning a bioprinter comprising a printhead within proximity of or in contact with the defect; and ejecting a bio-ink from the printhead onto the defect to form a bio-ink layer, thereby generating a bio-ink construct. Further provided are systems for bioprinting a bio-ink construct on an internal tissue defect during a minimally invasive surgery on an individual in need thereof, comprising a control system, an endoscope, and a bioprinter comprising a printhead.

A modular engineered tissue construct includes a plurality of fused self-assembled, scaffold-free, high-density cell aggregates. At least one cell aggregate includes a plurality of cells and a plurality of biocompatible and biodegradable nanoparticles and/or microparticles that are incorporated within the cell aggregates. The nanoparticles and/or microparticles acting as a bulking agent within the cell aggregate to increase the cell aggregate size and/or thickness and improve the mechanical properties of the cell aggregate as well as to deliver bioactive agents.