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.

Background/Aims:The fatigue, resistance, ambulation, illnesses, and loss of weight (FRAIL) scale is a screening tool for frailty status using a simple 5-item questionnaire. The aim of this study was to evaluate the clinical feasibility and validity of the Korean version of the FRAIL (K-FRAIL) scale.Methods:Questionnaire items were translated and administered to 103 patients aged ≥ 65 years who underwent a comprehensive geriatric assessment at the Seoul National University Bundang Hospital. In this cross-sectional study, the K-FRAIL scale was compared with the domains and the multidimensional frailty index of the comprehensive geriatric assessment. We also assessed the time required to complete the scale.Results:The participants’ mean age was 76.8 years (standard deviation [SD], 6.1), and 55 (53.4%) were males. The mean overall frailty index was 0.19 (SD, 0.17). For K-FRAIL-robust, prefrail, and frail patients, the mean frailty indices were 0.09, 0.18, and 0.34, respectively (p for trend < 0.001). A higher degree of impairment in the K-FRAIL scale was associated with worse nutritional status, poor physical performance, functional dependence, and polypharmacy. The number of items with impairment in the K-FRAIL scale was positively associated with the frailty index (B = 3.73, p < 0.001). The K-FRAIL scale could differentiate vulnerability from robustness with a sensitivity of 0.90 and a specificity of 0.33. Of all patients, 75 (72.8%) completed the K-FRAIL scale within < 3 minutes.Conclusions:The K-FRAIL scale is correlated with the frailty index and is a simple tool to screen for frailty in a clinical setting.

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.

This grading system is comprehensive and easily applicable with sufficient reproducibility. It can be used as a common nomenclature for research and discussions.

The changes that occur with disc degeneration progress from the normal state to an unstable phase with higher mobility and subsequently to an ankylosed stage. This study evaluated the contribution of different levels to the changes in overall motion that occur with degeneration.

HATDMSCs transfected with adeno-BMP-2 induce abundant bone formation and have a similar posterolateral spinal fusion in rats as similarly genetically modified HBMDMSCs. Both are potential strategies for spinal fusion and may be a more efficient method of obtaining spinal fusion over currently used grafting substances.

Object. Granulocyte—macrophage colony—stimulating factor (GM-CSF) is a potent hemopoietic cytokine that stimulates stem cell proliferation in the bone marrow and inhibits apoptotic cell death in leukocytes. Its effects in the central nervous system, however, are still unclear. The present study was undertaken to determine if GM-CSF can rescue neuronal cells from apoptosis and improve neurological function in a spinal cord injury (SCI) model. Methods. To study the effect of GM-CSF on apoptotic neuronal death, the authors used a staurosporine-induced neuronal death model in an N2A cell line (in vitro) and in a rat SCI model (in vivo). The N2A cells were preincubated with GM-CSF for 60 minutes before being exposed to staurosporine for 24 hours. To inhibit GM-CSF, N2A cells were pretreated with antibodies against the GM-CSF receptor for 60 minutes. Clip compression was used to induce SCI. Animals were treated with daily doses of GM-CSF (20 µg/day) for 5 days. The number of apoptotic cells in the spinal cord and neurological improvements were assessed. Pretreatment with GM-CSF was found to protect N2A cells significantly from apoptosis, and neutralizing antibodies for the GM-CSF receptors inhibited the rescuing effect of GM-CSF on apoptosis. In the rat SCI model, neurological function improved significantly in the GM-CSF—treated group compared with controls treated with phosphate-buffered saline. Terminal deoxynucleotidyl transferase—mediated deoxyuridine triphosphate nick-end labeling staining showed that GM-CSF administration reduced apoptosis in the injured spinal cord. Conclusions. Treatment of SCI with GM-CSF showed beneficial effects. Neuronal protection against apoptosis is viewed as a likely mechanism underlying the therapeutic effect of GM-CSF in SCI.

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