Intrathecal injection of autologous macrophages genetically modified to secrete BDNF by ex vivo electroporation improves hind limbs motor function after thoracic spinal cord injury in rats

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592168
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Ehime University
• Principal Investigator: OGATA Tadanori 愛媛大学, 医学部附属病院, 講師 (30291503)
• Co-Investigator(Kenkyū-buntansha): MORINO Tadao 愛媛大学, 医学部附属病院, 講師 (20380248) ; HORIUCHI Hideki 愛媛大学, 医学部附属病院, 助教(病院教員) (60598762)
• Project Period (FY): 2011 – 2013
• Keywords: Spinal cord injury / rat / macrophage / gene therapy / BDNF

Research Abstract

In order to develop an effective substance-delivery system for the treatment of spinal cord injury, we tried to overexpress BDNF protein in injury site by the transplantation of gene-modified autologous macrophages by lumbar puncture. Rat spinal cord injury was performed at the 11th thoracic vertebral level using a MASCIS impactor. Intrathecal injection of autologous macrophages genetically modified to secrete BDNF were injected into the subarachnoid space by lumbar puncture. Injected macrophages migrated and concentrated in the injured portion of the spinal cord and expressed GFP and BDNF proteins. The hind-limb function, evaluated by the BBB scale, in the BDNF-gene transferred animals, was significantly better than that in the vehicle animals from two weeks to eight weeks after the SCI. These results suggest that transplantation of gene-transfected autologous macrophages by lumbar puncture successfully improved hind-limb motor function via BDNF production after spinal cord injury.

Research Products

• [Journal Article] Autologous macrophages genetically modified by ex vivo electroporation and inserted by lumbar puncture migrate and concentrate in damaged spinal cord tissue : A safe and easy gene transfer method for the treatment of spinal cord injury (2012)
  • Author(s): Ogata, T., Morino, T., Horiuchi, H., Hino, M., Yamaoka, G., Miura H
  • Journal Title: Spine Surgery (K.J. Chung, Ed.) Pages: 137-148