Intrathecal Injection of Hepatocyte Growth Factor Gene-modified Marrow Stromal Cells Attenuates Neurologic Injury Induced by Transient Spinal Cord Ischemia in Rabbits

Abstract

Our previous studies showed that transfer of hepatocyte growth factor (HGF) gene or transplantation of marrow stromal cells (MSCs) remarkably attenuated neurologic injuries after spinal cord ischemia. We sought to investigate a novel neuroprotective strategy of transplantation of human HGF gene-modified MSCs on ischemic spinal cords. Human HGF gene was transferred into MSCs in vitro. The HGF gene-modified MSCs were transplanted by means of intrathecal injection. Two days later, spinal cord ischemia was induced by occlusion of the infrarenal aorta with a balloon catheter for 40 or 50 min. Hind-limb motor function was assessed during a 14-day recovery period with Tarlov criteria, and then histologic examination was performed. Human HGF was detected in the cerebrospinal fluid from 2 to 16 days after transplantation of HGF gene-modified MSCs. Compared with the controls, transplantation of HGF gene-modified MSCs or MSCs alone significantly improved the Tarlov scores 1, 2, 7, and 14 days after spinal cord ischemia of 40 or 50 min (P < 0.01, respectively) and increased the number of intact motor neurons in the lumbar spinal cord (P < 0.01, respectively). When the ischemic period was extended to 50 min, the Tarlov scores and the number of intact motor neurons of rabbits transplanted with HGF gene-modified MSCs were markedly higher than those of the rabbits transplanted with MSCs only (P < 0.05, respectively). Transplantation of HGF gene-modified MSCs induces powerful neuroprotection on spinal cords against ischemia-reperfusion injury and is more therapeutically efficient than transplantation of MSCs only.