Engineered human mesenchymal stem cells: a novel platform for skeletal cell mediated gene therapy

Background Human mesenchymal stem cells (hMSCs) are pluripotent cells that can differentiate to various mesenchymal cell types. Recently, a method to isolate hMSCs from bone marrow and expand them in culture was described. He re we report on the use of hMSCs as a platform for gene therapy aimed at bo ne lesions. Methods Bone marrow derived hMSCs were expanded in culture and infected wit h recombinant adenoviral vector encoding the osteogenic factor, human BMP-2 . The osteogenic potential of genetically engineered hMSCs was assessed in vitro and in vivo. Results Genetically engineered hMSCs displayed enhanced proliferation and o steogenic differentiation in culture. In vivo, transplanted genetically eng ineered hMSCs were able to engraft and form bone and cartilage in ectopic s ites, and regenerate bone defects (non-union fractures) in mice radius bone . importantly, the same results were obtained with hMSCs isolated from a pa tient suffering from osteoporosis. Conclusions hMSCs represent a novel platform for skeletal gene therapy and the present results suggest that they can be genetically engineered to expr ess desired therapeutic proteins inducing specific differentiation pathways . Moreover, hMSCs obtained from osteoporotic patients can restore their ost eogenic activity following human BMP-2 gene transduction, an important find ing in the future planning of gene therapy treatment for osteoporosis. Copy right (C) 2001 John Wiley & Sons, Ltd.