Compositions of mesenchymal stem cells to regenerate bone

摘要

The present invention encompasses an osteogenic composition comprising mesenchymal stem cells pre-cultured in the presence of an agent that accelerates canonical Wnt signaling therein. Also, provided are osteogenic compositions incorporated into a biocompatible gel. The present invention provides methods for treating bone degeneration or injury associated with a pathophysiological condition in a mammal or for accelerating repair of a skeletal injury in a mammal by administering to the mammal or contacting the site of injury with the osteogenic composition.

主权项

1. A population of pre-conditioned mesenchymal stem cells, wherein the population of pre-conditioned mesenchymal stem cells is produced by:
culturing mesenchymal stem cells in a conditioning medium lacking dexamethasone and comprising an effective amount of an inhibitor of peroxisome proliferator-activated receptor γ (PPAR-γ) for 5 to 14 days so as:
(a) to inhibit regulation of adipogenesis in the mesenchymal stem cells,(b) to induce the mesenchymal stem cells to exhibit:
(i) early or primitive osteoblastic characteristics without undergoing terminal differentiation,(ii) an upregulation in gene expression for collagen types I, III, V, VI, XI, and XII, and(iii) downregulation or depletion of cytosolic glycogen synthase kinase 3β, and(c) to not induce mineralization, wherein the pre-conditioned mesenchymal stem cells exhibit (a), (b), and (c) when removed from the conditioning medium.