Complete Spinal Cord Injury Treatment Using Autologous Bone Marrow Cell Transplantation and Bone Marrow Stimulation with Granulocyte Macrophage-Colony Stimulating Factor: Phase I/II Clinical Trial

Abstract

To assess the safety and therapeutic efficacy of autologous human bone marrow cell (BMC) transplantation and the administration of granulocyte macrophage-colony stimulating factor (GM-CSF), a phase I/II open-label and nonrandomized study was conducted on 35 complete spinal cord injury patients. The BMCs were transplanted by injection into the surrounding area of the spinal cord injury site within 14 injury days (n ‫؍‬ 17), between 14 days and 8 weeks (n ‫؍‬ 6), and at more than 8 weeks (n ‫؍‬ 12) after injury. In the control group, all patients (n ‫؍‬ 13) were treated only with conventional decompression and fusion surgery without BMC transplantation. The patients underwent preoperative and follow-up neurological assessment using the American Spinal Injury Association Impairment Scale (AIS), electrophysiological monitoring, and magnetic resonance imaging (MRI). The mean follow-up period was 10.4 months after injury. At 4 months, the MRI analysis showed the enlargement of spinal cords and the small enhancement of the cell implantation sites, which were not any adverse lesions such as malignant transformation, hemorrhage, new cysts, or infections. Furthermore, the BMC transplantation and GM-CSF administration were not associated with any serious adverse clinical events increasing morbidities. The AIS grade increased in 30.4% of the acute and subacute treated patients (AIS A to B or C), whereas no significant improvement was observed in the chronic treatment group. Increasing neuropathic pain during the treatment and tumor formation at the site of transplantation are still remaining to be investigated. Long-term and large scale multicenter clinical study is required to determine its precise therapeutic effect.

Co-transplantation of autologous bone marrow mesenchymal stem cells and Schwann cells through cerebral spinal fluid for the treatment of patients with chronic spinal cord injury: safety and possible outcome

“…These findings are in accordance with the results of other studies in patients with chronic spinal cord injuries. 18 Despite improvement in ISNCSCI scores in some of the patients, SCIM scores remained unchanged in the course of the study. This subject may contribute to the functional nature of this scale.…”

“…15 Previously, SCs and MSCs have been applied in some studies, but individually and through direct injection or lumbar puncture, for which the safety appliance was identified. 13,17,18 The safety of cotransplantation of autologous SCs and bone marrow MSCs for the treatment of patients with chronic spinal cord injury through direct transplantation of this combination into the injured area has been documented in our previous study. 5 In this study, a mixture of SCs and bone marrow MSCs were administered intrathecally in six patients who suffered from complete traumatic spinal cord injury.…”

“…23,24 In our study, neuropathic pain and muscle spasm increased in 50% of the patients, which is more than what has been observed in our study and other previous studies. 5,18 In accordance with a small number of patients and lack of a control group, we could not say with confidence that intrathecal administration of this mixture of cells may increase the risk of neuropathic pain or muscle spasm development. Studies with larger volume sizes and control group consideration in phase II are required for definitive comment on this subject.…”

The Intrathecal Infusion of Mesenchymal Stem Cells into Healthy Rabbits is Safe and Devoid of Neurological or Clinical Complications

“…A low (0.3 x 10 6 MSC/kg) and a high cell dose (0.6 x 10 6 MSC/kg) product was prepared and transferred to 1 cc syringes. When translated to a clinical setting, the above doses will be comparable to the infusion of 0.1 x 10 6 /kg to 2.5 x 10 6 MSC /kg, which is similar to the range of MSC utilized or proposed in clinical studies [21,[24][25][26].…”

Updates on stem cells and their applications in regenerative medicine

“…The patients showed improvement in both sensory and motor functions. Similarly, Yoon et al (2007) treated 35 patients with complete spinal injuries at different time points following injury. No complications were observed and some improvements were obtained in the patients treated few weeks following injury.…”