Saturday, March 3, 2001
Using ex-vivo gene therapy, they transduced mouse skeletal muscle cells to produce rhBMP-2. Without breaching the dura, a 5-mm non-healing skull defect was surgically created in 40 SCID mice. Approximately 0.5-1.0 x 106 transduced cells producing rhBMP-2 were implanted into the skull defects using a collagen sponge matrix. The mice were sacrificed at two weeks and four weeks, and skulls were analyzed digitally as well as by histological staining.
Mice treated with mouse muscle cells producing BMP-2 showed >85 percent healing of the skull defect by two-weeks and >95 percent healing by four-weeks. None of the control groups ever showed more than 30 percent healing of the defects. As analyzed by Von Kossa staining, new bone formation in mice treated with transduced muscle cells seemed to emerge both from the dura as well as the adjacent bone edge. The control group did not show any mineralized bone formation.
Thus, the researchers say ex-vivo gene therapy methods using skeletal muscle cells is effective in treating non-healing bone defects in SCID mice. Clinically, skeletal muscle is easily obtainable by muscle biopsies.
Genetically introducing BMP-2 by ex-vivo methods reduces harmful effects that the virus may have on the host. This method of implanting bone inductive muscle cells may be an effective method to treat a multitude of orthopaedic ailments, including segmental bone defects and severe fractures.
The coauthors of the study are Joon Yung Lee, MD; Douglas Musgrave, MD; Dalip Pelinkovic, MD; Arvydas Usas, MD; James Cummins, BS; Freddie Fu, MD; and Johnny Huard, PhD, all of the department of orthopaedic surgery, University of Pittsburgh, Pa.; and Kazumasa Fukushima, MD, department of orthopaedic surgery and sports medicine, School of Medicine, Nihon University, Tokyo, Japan; and Paul Robbins, PhD, department of molecular genetics and biochemistry, University of Pittsburgh, Pa.
|2001 Academy News March 3 Index C|
Last modified 16/February/2001 by IS