INDUCTION OF BONE-FORMATION USING A RECOMBINANT ADENOVIRAL VECTOR CARRYING THE HUMAN BMP-2 GENE IN A RABBIT SPINAL-FUSION MODEL

Bone marrow-derived mesenchymal stem cells are pluripotential cells th at have the capacity to differentiate into an osteoprogenitor line. It has been demonstrated that BMP-2 can enhance this differentiation pro cess. In an attempt to prolong the transforming effect of BMP-2, we us ed an adenoviral. vector carrying the human BMP-2 gene to transduce ma rrow-derived mesenchymal stem cells of New Zealand white rabbits. Assa ys on tissue culture demonstrated that these cells indeed produced the BMP-2 protein. These transduced stem cells were then autologously rei mplanted into the donor rabbits. The cells were placed in the intertra nsverse process area of five rabbits. In one out of the five rabbits, this resulted in the production of new bone which was demonstrable on both radiographic and histologic examination. We conclude that it is p ossible to successfully transduce mesenchymal stem cells with the gene for BMP-2 such that these cells will produce the BMP-2 protein in vit ro. Further, the transduction results in transformation of these cells into an osteoprogenitor line capable of producing bone in vivo. These data suggest the feasibility of employing gene therapy using recombin ant adenoviral vectors as a tool for enhancing spine fusion. Further w ork to improve the fidelity and longevity of the gene transfer is warr anted.