K. N. Kim

Functional recovery after human umbilical cord blood cells transplantation with brain-derived neutrophic factor into the spinal cord injured rat

SummaryThere have been many efforts to recover neuronal function from spinal cord injuries, but there are some limitations in the treatment of spinal cord injuries.The neural stem cell has been noted for its pluripotency to differentiate into various neural cell types. The human umbilical cord blood cells (HUCBs) are more pluripotent and genetically flexible than bone marrow neural stem cells. The HUCBs could be more frequently used for spinal cord injury treatment in the future.Moderate degree spinal cord injured rats were classified into 3 subgroups, group A: media was injected into the cord injury site, group B: HUCBs were transplanted into the cord injury site, and group C: HUCBs with BDNF (Brain-derived neutrophic factor) were transplanted into the cord injury site. We checked the BBB scores to evaluate the functional recovery in each group at 8 weeks after transplantation. We then, finally checked the neural cell differentiation with double immunofluorescence staining, and we also analyzed the axonal regeneration with retrograde labelling of brain stem neurons by using fluorogold. The HUCBs transplanted group improved, more than the control group at every week after transplantation, and also, the BDNF enabled an improvement of the BBB locomotion scores since the 1 week after its application (P<0.05). 8 weeks after transplantation, the HUCBs with BDNF transplanted group had more greatly improved BBB scores, than the other groups (P<0.001). The transplanted HUCBs were differentiated into various neural cells, which were confirmed by double immunoflorescence staining of BrdU and GFAP & MAP-2 staining. The HUCBs and BDNF each have individual positive effects on axonal regeneration. The HUCBs can differentiate into neural cells and induce motor function improvement in the cord injured rat models. Especially, the BDNF has effectiveness for neurological function improvement due to axonal regeneration in the early cord injury stage. Thus the HUCBs and BDNF have recovery effects of a moderate degree for cord injured rats.

Clinical and radiological results following cervical arthroplasty

SummaryBackground. This was a retrospective study of clinical and radiological results of cervical arthroplasty using the Bryan cervical disc prosthesis to evaluate the efficacy of arthroplasty in clinical applications.Methods. A total of 46 patients underwent arthroplasty of a single level using the Bryan disc prosthesis. Clinical outcome was assessed using the visual analogue scale (VAS) and the neck disability index (NDI). All patients were evaluated using preoperative and postoperative static cervical spine radiographs to compare cervical sagittal balance. Dynamic cervical spine radiographs were used to compare movement at the level of the procedure, movement at the adjacent level and movement of the whole cervical spine.Findings. With the exception of four patients with aggravated neck pain, the NDI and VAS scores decreased significantly in late follow-up evaluations. The range of movement of the whole cervical spine, the functional segmental unit, and the adjacent segments were preserved after arthroplasty. The sagittal alignment of the cervical spine showed kyphosis after surgery but restored lordosis at a later time. The postulated cause of kyphotic changes include “over-milling” at the dorsal endplate, inappropriate angle of disc insertion, structural absence of lordosis in the Bryan disc, removal of posterior longitudinal ligament, and pre-existing kyphosis.Conclusions. Arthroplasty using the Bryan disc appears to be safe and provided a favorable preliminary clinical and radiological outcome. Postoperative kyphosis can be prevented by understanding the biomechanical properties of the Bryan disc. Future studies will need to address the association between postoperative kyphosis, clinical outcome and adjacent segment disease.

Intermediate filament nestin expressions in human cord blood monocytes (HCMNCs).

Summary¶Objects. Nestin is an intermediate protein and a well-known specific neural stem cell antigen. Some bone marrow stem cells can generate not only blood cells but also neurons and glial cells under specific culture conditions. Furthermore, in vitro cultured bone marrow stem cells also express nestin antigen. However, it is unclear whether cord blood cells also differentiate into neural cells or not. In this study, we investigated the expression of nestin on human cord blood monocytes (HCMNCs) and we discuss the relevance of this finding upon future therapeutic applications of HCMNCs in neurological diseases. Methods. HCMNCs were prepared from normal placenta after full-term normal delivery. Immunocytochemical staining and reverse transcriptase polymerase chain reaction (RT-PCR) for nestin and CD133 antigen were performed to confirm nestin and CD133 antigen expression in the HCMNCs. Results. Some nestin expressing HCMNCs were found. Immunocytochemical staining showed that some of the blood stem cell marker CD133 expressing cells co-expressed nestin. RT-PCR demonstrated nestin and CD133 mRNA in HCMNCs, but not in adult blood monocytes. Approximately, 60 ± 8% of CD133 expressing cells expressed nestin. Conclusion. In the present study, we found that more than 60% of CD133 expressing HCMNCs also express nestin antigen in their cytoplasm, which supports the idea that cord blood stem cells can adopt a neuronal fate.

Surgical management of spinal cord haemangioblastoma

SummaryBackground. The surgical management of spinal cord haemangioblastomas is distinct from that of other benign spinal cord tumours and optimal surgical strategy is still being determined because of the rarity of the condition. The aim of this study is to investigate factors that affect the outcome of surgical management. Patients and methods. We retrospectively analysed 24 operations for symptomatic spinal cord haemangioblastomas in 20 patients. Clinical features and surgical results were investigated by medical record review, telephone interviews, angiographic images, and magnetic resonance images (MRI). The mean follow-up period was 5.6 years (range 6 months to 13.6 years). Results. Patients with cystic components showed pre-operative motor weakness and sensory change more commonly than those without cystic components. Post-operative function scale had a positive correlation with pre-operative function (R2 = 0.727; p < 0.001) and no correlation with the extent of the surgery. All subtotally removed tumours recurred, whereas totally removed tumours recurred in only 3 patients. Conclusion. The cystic component of spinal cord haemangioblastomas is responsible for symptom generation and is helpful for dissecting tumours. Post-operative functional status is determined by pre-operative functional status. Total removal is feasible by using the correct surgical technique and is recommended to prevent recurrence.

Cervical arthroplasty in a patient with Klippel-Feil syndrome

SummaryThis is the first published report of a patient with Klippel-Feil syndrome treated with cervical arthroplasty. A 36-year-old man presented with posterior neck pain and myelopathic symptoms. A radiograph demonstrated congenital fusion of the vertebral bodies at C2–3, C4–5 and C5–6. On MRI, the spinal cord was compressed by a protruding cervical disc and bony spurs at C6–7. After anterior discectomy and decompression of the spinal cord at the C6–7 level, the disc was replaced with the Bryan cervical disc system (Medtronic Sofamor Danek, Memphis, TN, USA) to restore normal motion. The absence of adjacent segment degeneration and the preservation of cervical motion were noted 2 years after surgery. Arthroplasty may be performed in selected patients with Klippel-Feil syndrome in order to restore motion and to prevent degeneration of the adjacent segment by reducing hypermobility.

Progressive collapse of PMMA-augmented vertebra: a report of three cases.

Vertebroplasty using polymethylmethacrylate (PMMA) for augmentation is accepted as a safe and effective treatment for vertebral compression fracture. However, various complications related to PMMA vertebroplasty have recently been reported. We experienced three cases with progressive collapse of PMMA-augmented vertebra. Collapse progressed after augmentation in cases where PMMA conglomerated without contiguous bone interdigitation. A high viscosity of the PMMA preparation and vertebral body cavitory lesion may play a role in progressive vertebral collapse. To avoid this complication, bone cement should be injected sufficiently and permeate to contiguous bone to create strong support and anchorage.

Outcome of surgery for a symptomatic herniated thoracic disc in relation to preoperative characteristics of the disc

SummaryBackground. This report presents general information on herniated thoracic discs, their clinical manifestations as well as surgical treatment, and examines the differences in the surgical outcome based on disc characteristics.Methods. This study includes 33 thoracic discectomies in 29 patients with a ventrally situated herniated thoracic disc reaching to the thoracic cord. Using preoperative computed tomography scanning and magnetic resonance imaging, the direction of the disc was classified as either central or lateral, and disc consistency classified as either soft or hard. Clinical outcome was assessed according to the Japanese Orthopedic Association (JOA) Score for thoracic myelopathy. The score was obtained by analysing motor, sensory and bladder function. Recovery rate was assessed, comparing preoperative and postoperative status based on disc characteristics. The correlations between outcome, symptom duration and recovery rate were also investigated.Findings. Clinical outcome according to the JOA Score showed significant postoperative improvement, increasing from 7.0 ± 3.1 points to 8.2 ± 2.7 points postoperatively (p < 0.01). The mean recovery rate was 12.4 ± 56.9%, and 16 patients (55.2%) showed improvement. In the soft disc group, there was improvement in all categories, but the hard disc group showed no improvement. The central disc group showed improvement in sensory function, but the lateral disc group showed little improvement. Regression analysis revealed a statistically significant correlation between the preoperative and postoperative score, symptom duration and recovery rate.Conclusions. Clinical outcome after surgery of a herniated thoracic disc proved successful, especially when the disc was considered to have a soft consistency. In order to decide the optimal surgical strategy and prospective surgical outcome, disc characteristics, including consistency and direction of prolapse should be considered preoperatively.

Association between VEGF and eNOS gene polymorphisms and lumbar disc degeneration in a young Korean population.

Disturbances in blood flow to intervertebral discs (IVD) play an important role in IVD degeneration. Vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) are extremely important angiogenic factors for vasodilation and neovascularization. We investigated the relationship between single nucleotide polymorphisms (SNPs) of the VEGF and eNOS genes and genetic susceptibility to lumbar IVD degeneration in a young adult Korean population. Two hundred and forty-one participants (aged 18 to 30 years), with or without low back pain, were selected for the study. Magnetic resonance imaging was made of the lumbar spine in all participants. The patient group (N = 102) had low back pain clinically and lumbar IVD degeneration radiographically. The control group (N = 139) included subjects with and without low back pain; all were negative radiographically for lumbar IVD degeneration. Using PCR-RFLP analysis, we analyzed VEGF (-2578C>A, -1154G>A, -634G>C, and 936C>T) and eNOS (-786T>C, 4a4b and 894G>T) SNPs. We made combined analyses of the genes and performed haplotype analyses. There were no significant differences in the genotype distribution of polymorphisms of VEGF and eNOS genes among patients and controls. However, the frequency of VEGF -2578CA +AA/-634CC combined genotypes was significantly higher in patients when compared with controls [odds ratio (OR) = 21.00; 95% confidence interval (CI) = 2.590- 170.240]. The frequencies of the -2578A/-1154A/-634C/936C (OR = 3.831; 95%CI = 1.068-13.742), -2578A/-1154A/-634C (OR = 3.356; 95%CI = 1.198-9.400), and -2578A/-634C/936C (OR = 10.820; 95%CI = 2.811-41.656) haplotypes were also significantly higher in patients than in controls. We conclude that the combined genotype VEGF -2578CA+AA/-634CC is a possible risk factor for IVD degeneration and the VEGF -2578A/-1154A/-634C/936C haplotype may increase the risk for development of IVD degeneration. Furthermore, the VEGF -634C allele appears to be associated with susceptibility to IVD degeneration.

Transcriptomic Analysis of Insulin-Sensitive Tissues from Anti-Diabetic Drug Treated ZDF Rats, a T2DM Animal Model

Gene expression changes have been associated with type 2 diabetes mellitus (T2DM); however, the alterations are not fully understood. We investigated the effects of anti-diabetic drugs on gene expression in Zucker diabetic fatty (ZDF) rats using oligonucleotide microarray technology to identify gene expression changes occurring in T2DM. Global gene expression in the pancreas, adipose tissue, skeletal muscle, and liver was profiled from Zucker lean control (ZLC) and anti-diabetic drug treated ZDF rats compared with those in ZDF rats. We showed that anti-diabetic drugs regulate the expression of a large number of genes. We provided a more integrated view of the diabetic changes by examining the gene expression networks. The resulting sub-networks allowed us to identify several biological processes that were significantly enriched by the anti-diabetic drug treatment, including oxidative phosphorylation (OXPHOS), systemic lupus erythematous, and the chemokine signaling pathway. Among them, we found that white adipose tissue from ZDF rats showed decreased expression of a set of OXPHOS genes that were normalized by rosiglitazone treatment accompanied by rescued blood glucose levels. In conclusion, we suggest that alterations in OXPHOS gene expression in white adipose tissue may play a role in the pathogenesis and drug mediated recovery of T2DM through a comprehensive gene expression network study after multi-drug treatment of ZDF rats.

Rapid recovery of tissue hypoxia by cotransplantation of endothelial cells.

Disruption of blood vessels caused by a spinal cord injury leads to tissue hypoxia. This hypoxic condition reduces the survival of transplanted stem cells, consequentially decreasing the effectiveness of stem cell therapy. In this study, we investigated the correlation between angiogenesis and the survival of transplanted neural stem cells in a spinal cord injury model. Hypoxia-specific luciferase-expressing neural stem cells (EpoSV-Luc NSC) were used as a tool for the detection of hypoxia caused by a spinal cord injury. In vivo, angiogenesis by cotransplantation of endothelial cells quickly recovered tissue hypoxia caused by a spinal cord injury. As a result, cotransplantation of endothelial cells improved the survival of neural stem cells transplanted into the injured spinal cord.