Tissue engineering of large bone defects is approached through implantation of autologous osteogenic cells, named multipotent stromal cells or mesenchymal stem cells (MSCs). The ability of human MSCs to differentiate into adipogenic, chondrogenic, osteogenic, and myogenic lineages has generated a great deal of potential clinical use in regenerative medicine and tissue engineering in the past decade. Although animal-derived MSCs successfully bridge large bone defects, models for ectopic bone formation as well as recent clinical trials demonstrate that bone formation by human MSCs is inadequate. Predifferentiation of human MSCs into the osteogenic lineage in vitro during the expansion phase before implantation offers an opportunity to improve their in vivo performance.

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Mesenchymal stem/progenitor cells (MSCs) can differentiate into adipocytes, muscle cells, osteoblasts, or cartilage and possess potential for tissue repair in patients with osteoporosis, diseased joints, and myocardial infarction. Many groups have investigated strategies involving the infusion of MSCs for the purpose of regenerative therapy; however, problems concerning MSC homing to diseased sites and the use of allogeneic MSCs have limited this approach. Therefore, the ability to use pharmacological agents to induce the differentiation of resident MSCs toward a certain lineage in vivo is an important therapeutic goal. In a recent study [1], the authors report that bortezomib, a clinically available proteasome inhibitor active against myeloma, induces the differentiation of MSCs into osteoblasts, resulting in new bone formation.

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