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

Abstract

Background: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. Methods: 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. Results: 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 Ͻ 0.01, respectively) and increased the number of intact motor neurons in the lumbar spinal cord (P Ͻ 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 Ͻ 0.05, respectively). Conclusions: 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. P ARAPLEGIA remains a major devastating and unpredictable complication after surgical repair of descending and thoracoabdominal aortic aneurysms. This complication is attributed primarily to temporary or permanent intervention of the blood supply of spinal cords. Regardless of the progress with surgical techniques and pharmacologic interventions, the incidence of paraplegia is still high at 6.6 -8.3% in patients with extent II thoracoabdominal aortic aneurysms. 1,2Hepatocyte growth factor (HGF) was originally found from plasma and serum as a molecule that could stimulate DNA synthesis in rat and human hepatocytes.3 HGF has been identified as a potential angiogenetic factor. 4 Moreover, HGF also plays a role as a neurotrophic and survival factor to maintain the structure and function of the nervous system. 5 HGF has been reported to induce versatile neuroprotective effects both in vitro and in vivo. 6 In our previous report, transfer of human HGF gene has been shown to attenuate the neurologic injury caused by spinal cord ischemia, as evidenced by the improvement of hind-limb motor function and the protection of the motor neurons. Address correspondence to Dr. Jiang: Department of Anesthesiology, First Affiliated Hospital, China Medical University, Shenyang, P. R. China, 110001. jiangsophie@hotmail.com. Information on purchasing reprints may be found at www.anesthesiolo...

Intrathecal transplantation of stem cells by lumbar puncture for thoracic spinal cord injury in the rat

“…[2][3][4] The intrathecal technique of cell injection has also been used in other animal models. [5][6][7] However, the phenotype of LP transplanted neural stem/progenitor cells (NSPCs) and bone marrow-derived mesenchymal stromal cells (BMSCs) and their spatial distribution along the intact and injured spinal cord has not been reported or quantitated. LP is a minimally invasive method of cell delivery, and stem cells may be well suited for LP transplantation because of their responsiveness to signals from the injured CNS.…”

Human Mesenchymal Stem Cells Promote Ischemic Repairment and Angiogenesis of Diabetic Foot Through Exosome miRNA-21-5p

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“…Hepatocyte growth factor may inhibit apoptosis, stimulate axonal outgrowth, and facilitate recovery of motor function. 11,12 In the present case, hepatocyte growth factor in bone marrow mononuclear cells may have contributed to recovery of motor function. In addition, the CD34+ cells that were present may confer protection against nerve injury, supply several nerve growth factors, and facilitate spinal cord T2-weighted image showed signal hyperintensity (arrow head) along 3 vertebral bodies centered at T12.…”