Treatment of Complete Spinal Cord Injury Patients by Autologous Bone Marrow Cell Transplantation and Administration of Granulocyte-Macrophage Colony Stimulating Factor

Abstract

Transplantation of bone marrow cells into the injured spinal cord has been found to improve neurologic functions in experimental animal studies. However, it is unclear whether bone marrow cells can similarly improve the neurologic functions of complete spinal cord injury (SCI) in human patients. To address this issue, we evaluated the therapeutic effects of autologous bone marrow cell transplantation (BMT) in conjunction with the administration of granulocyte macrophage-colony stimulating factor (GM-CSF) in six complete SCI patients. BMT in the injury site (1.1 x 10(6) cells/microL in a total of 1.8 mL) and subcutaneous GM-CSF administration were performed on five patients. One patient was treated with GM-CSF only. The follow-up periods were from 6 to 18 months, depending on the patients. Sensory improvements were noted immediately after the operations. Sensory recovery in the sacral segment was noted mainly 3 weeks to 7 months postoperatively. Significant motor improvements were noted 3 to 7 months postoperatively. Four patients showed neurologic improvements in their American Spiral Injury Association Impairment Scale (AIS) grades (from A to C). One patient improved to AIS grade B from A and the last patient remained in AIS grade A. No immediate worsening of neurologic symptoms was found. Side effects of GMCSF treatment such as a fever (>38 degrees C) and myalgia were noted. Serious complications increasing mortality and morbidity were not found. The follow-up study with magnetic resonance imaging 4-6 months after injury showed slight enhancement within the zone of BMT. Syrinx formation was not definitely found. BMT and GM-CSF administration represent a safe protocol to efficiently manage SCI patients, especially those with acute complete injury. To demonstrate the full therapeutic value of this protocol, long-term and more comprehensive case-control clinical studies are required.

Autologous mucosal transplant in chronic spinal cord injury: an Indian Pilot Study

“…To date, there is no evidence of any cellular transplant for SCI having completed a valid clinical trial program. Amongst the few published human clinical studies [1][2][3][4][5][6][7][8][9] most have either been pilot studies or had limitations with respect to the study design, number of participants and/or duration of follow-up. This prompted us to plan a more rigorous human study to assess outcomes after cell transplant in participants with complete motor loss after SCI (American Spinal Injury Association (ASIA) Impairment Scale (AIS) A and B).…”

Bone marrow-derived mesenchymal stromal cells for the repair of central nervous system injury

“…In 2005, Park et al 95 reported the first trial of MSCs in humans with spinal cord injury and showed that humans treated with autologous whole bone marrow transplanted into the site of spinal cord injury, along with i.v. granulocyte-macrophage (GM)-CSF, showed improved neurological function, but the full therapeutic value of this protocol is still being investigated.…”

Migration, fate and in vivo imaging of adult stem cells in the CNS

“…There have been no complications during patient follow-up for 2-3 years after implantation. A recent clinical study was performed by Park et al 58 on six patients with SCI. A combination of autologous BMCs implanted as early as 7 days after SCI and subsequent repetitive mobilization of BMCs with granulocyte macrophage-colony-stimulating factor (GM-CSF) resulted in five out of six patients showing improved motor and/or sensory function.…”