571. Increasing BMP Responsiveness in Human Mesenchymal Stem Cells In-Vitro by Delivery of the Osteoinductive LMP-1 Gene

BMPs promote the differentiation of osteoprogenitor cells, and also induce osteogenesis in bone marrow stromal cells (MSCs) from rats and mice. However, compared to results with animal models, BMPs are relatively inefficient in inducing human MSCs to undergo osteogenesis, and are much less effective in promoting bone formation in human clinical trials. Previous studies indicated that, while human MSCs respond to Dex with elevated levels of the osteoblast marker alkaline phosphatase, most isolates of human MSCs fail to show alkaline phosphatase induction in response to BMP-2,|[minus]|4 and |[minus]|7. LIM Mineralization Protein-1 (LMP-1) is an intracellular regulatory protein that can induce the expression of multiple BMPs and promote osteoblast differentiation in vitro and in vivo. The purpose of this study was: 1) To determine if delivery of LMP-1 can increase the responsiveness of human MSCs to BMP-2 as evidenced by increasing osteoblastic markers, and 2) To determine if delivery of LMP-1 can potentiate BMP-2 induction of mineralization by human MSC cultures.