Meta-analysis of the quantitative assessment of lower extremity motor function in elderly individuals based on objective detection.

OBJECTIVE: To avoid deviation caused by the traditional scale method, the present study explored the accuracy, advantages, and disadvantages of different objective detection methods in evaluating lower extremity motor function in elderly individuals. METHODS: Studies on lower extremity motor function assessment in elderly individuals published in the PubMed, Web of Science, Cochrane Library and EMBASE databases in the past five years were searched. The methodological quality of the included trials was assessed using RevMan 5.4.1 and Stata, followed by statistical analyses. RESULTS: In total, 19 randomized controlled trials with a total of 2626 participants, were included. The results of the meta-analysis showed that inertial measurement units (IMUs), motion sensors, 3D motion capture systems, and observational gait analysis had statistical significance in evaluating the changes in step velocity and step length of lower extremity movement in elderly individuals (P < 0.00001), which can be used as a standardized basis for the assessment of motor function in elderly individuals. Subgroup analysis showed that there was significant heterogeneity in the assessment of step velocity [SMD=-0.98, 95%CI(-1.23, -0.72), I2 = 91.3%, P < 0.00001] and step length [SMD=-1.40, 95%CI(-1.77, -1.02), I2 = 86.4%, P < 0.00001] in elderly individuals. However, the sensors (I2 = 9%, I2 = 0%) and 3D motion capture systems (I2 = 0%) showed low heterogeneity in terms of step velocity and step length. The sensitivity analysis and publication bias test demonstrated that the results were stable and reliable. CONCLUSION: observational gait analysis, motion sensors, 3D motion capture systems, and IMUs, as evaluation means, play a certain role in evaluating the characteristic parameters of step velocity and step length in lower extremity motor function of elderly individuals, which has good accuracy and clinical value in preventing motor injury. However, the high heterogeneity of observational gait analysis and IMUs suggested that different evaluation methods use different calculation formulas and indicators, resulting in the failure to obtain standardized indicators in clinical applications. Thus, multimodal quantitative evaluation should be integrated.

Hip subluxation in children with spinal cord injury: Incidence and influencing factors.

OBJECTIVE: Hip subluxation is a common complication in children with spinal cord injury. This study aimed to investigate the incidence and influencing factors of hip subluxation and discuss prevention strategies. METHODS: Medical records of children with spinal cord injury were reviewed. The inclusion criteria were as follows: (1) the patient was younger than 18 years old when injured; (2) absence of traumatic or congenital pathological changes of the hip at the time of injury. The migration percentage and acetabular index were selected to evaluate hip stability and acetabulum development. Influencing factors of sex, age, injury duration, severity, level, and spasticity were analyzed. RESULTS: A total of 146 children were enrolled. Twenty-eight children presented with hip subluxation and were significantly younger at the time of injury than those with normal hips (P = 0.002). The incidence of hip subluxation increased with the prolonged injury duration. Injury before age 6, complete injury, and flaccid lower extremities were significant influencing factors (P = 0.003, 0.004, and 0.015, respectively). The risk of hip subluxation decreased by 18% for every year older in injury age (P = 0.031) and decreased by 85% in children with spasticity (P = 0.018) than those without. However, the risk of hip subluxation in children with injury duration longer than 1 year was 7.1 times higher than those with shorter injury duration (P < 0.001). CONCLUSIONS: The incidence of hip subluxation in children with spinal cord injury increased with the injury duration. Younger children had immature hip development. Due to complete injury and flaccid muscle, lack of protection around the hip may lead to subluxation. Follow-up and prevention of hip subluxation need the joint effort of medical staff and families.

Novel Physical Examination Tests for the Diagnosis of Chronic Sacroiliac Joint Dysfunction and Differentiate It From Lumbar Disc Herniation.

BACKGROUND: Traditional sacroiliac joint (SIJ) provocation tests have been used to diagnose SIJ pain. However, this can simply be changed to chronic SIJ dysfunction (cSIJD) manifests as mechanical changes in the pelvis and lower extremities in addition to pain. A novel composite of physical examinations based on the iliac pronation, pubic tubercle tenderness, and plantar fascia tenderness tests (IPP triple tests) was designed for the diagnosis of cSIJD. OBJECTIVES: To evaluate IPP triple tests in the diagnosis of cSIJD and differential diagnosis from lumbar disc herniation (LDH) in comparison with traditional provocation tests. STUDY DESIGN: Prospective single-blind controlled study. SETTING: This study was conducted at the Department of Spine and Spinal Cord Surgery of China Rehabilitation Research Center in Beijing, China. METHODS: One hundred and sixty-six patients were assigned into the cSIJD group, LDH group, or healthy control group. The cSIJD diagnosis was confirmed by SIJ injection. The diagnosis of LDH was confirmed according to the 2014 North American Spine Association diagnosis and treatment guidelines for LDH. All patients were examined with IPP triple tests and traditional provocation tests. The sensitivity, specificity, positive and negative likelihood ratios, and areas under the curve (AUCs) were used to evaluate the diagnostic accuracy of the composites or single of the IPP triple tests, and traditional provocation tests. The Delong's test was used for the comparison among AUCs. The kappa analysis was used for the IPP triple tests and traditional provocation tests compared with the reference standard (REF). The independent t test and chi-square test were used to analyze the influence factors (i.e., age, gender), and group on diagnostic accuracy. RESULTS: There was no statistical difference in gender (chi-squared = 0.282, P = 0.596) and age (F = 0.096, P = 0.757) between the 3 groups. The AUC of the iliac pronation test was 0.903 when it was used alone; the AUC of the novel composites of the IPP triple tests was 0.868 (95% confidence interval [CI] = 0.802-0.919); and the diagnostic accuracy of the traditional provocation test was relatively low (AUC = 0.597, 95% CI = 0.512-0.678). The diagnostic accuracy of the IPP triple tests was higher than that of the traditional provocation test, P < 0.05. Kappa consistency comparison showed that the kappa value between the IPP triple tests and the REF was 0.229, the kappa between the traditional provocation test and the REF was 0.052. The age of the patients with inaccurate diagnosis was higher than that of the patients with accurate diagnosis in both methods (traditional tests, P = 0.599; IPP:P = 0.553). Different types of diseases (groups) affect the accuracy of diagnosis, the proportion of inaccuracy of traditional provocation tests was higher than that of the IPP triple tests (77.8% vs 23.6%) in cSIJD, while the 2 methods have high differential diagnostic accuracy in LDH (96.77%) and control groups (97.56%). LIMITATIONS: Small size of LDH patients and differences in physical tests among examiners. CONCLUSIONS: The novel composites of IPP triple tests have higher accuracy than the traditional provocation tests in diagnosing cSIJD and both have good accuracy in differentiating cSIJD from LDH. IPP triple tests may be an alternative physical examination for clinical screening of cSIJD.

Prognosis of traumatic spinal cord injury in children: Follow-up of 86 patients.

PURPOSE: The long-term situation of children with spinal cord injury (SCI) was investigated, and suggestions for helping them better return to the society were provided. METHODS: SCI patients less than 18 years old hospitalized in Beijing Boai Hospital from January 2011 to December 2020 were retrospectively analyzed. Information including motor function, complications, characteristic changes, self-care abilities, school attendance and social participation were collected by telephone interview and electronic questionnaire. All the answers were statistically analyzed. RESULTS: A total of 86 cases were enrolled, 77 girls and 9 boys, with a median injury age of 6 years and 2 months. The follow-up time was 3-130 months. The main cause of trauma in these children was sport injury (66.3%), the thoracic spinal cord was involved the most (91.9%), and complete SCIs accounted for the majority (76.7%). In terms of complications, children with complete SCIs were more likely to have urinary incontinence, constipation and characteristic changes (p < 0.05); whereas the incomplete SCIs often have spasticity (p < 0.05). As to the daily living abilities, children with incomplete lumbar SCIs were more capable to accomplish personal hygiene, transfer, and bathing independently than those with complete injuries, or cervical/thoracic SCIs, respectively (p < 0.05). Moreover, children older than 9 years care more able to dress and transfer independently than the youngers (p < 0.05). Wheelchair users accounted for 84.9% and more than half of them were able to propel wheelchair independently, and those who move passively in wheelchairs were mostly introverted kids (p < 0.05). Almost all (93.8%) children with incomplete injuries were able to walk independently. Most (79.1%) children continued to attending school, and 41.9% participated in interest classes. Unfortunately, 67.4% of the children spent less time playing with their peers than before the injury. CONCLUSION: SCIs impair physical structures and function of children, affect their independence in daily living, and restrict school attendance and social interaction. Comprehensive rehabilitation after injury is a systematic work. Medical staff and caregivers should not only pay attention to neurological function, but also help them improve self-care abilities. It is also important to balance rehabilitation training and school work and social participation.

Clinical characteristics of pediatric traumatic spinal cord injury in China: A single center retrospective study.

OBJECTIVE: To investigate the clinical characteristics of children with traumatic spinal cord injury (SCI) admitted to a research rehabilitation center between 2011 and 2020, with a view to generate crucial data for understanding and prevention of pediatric traumatic SCI. DESIGN: Retrospective cohort study. SETTING: The National Rehabilitation Research Center of China, Beijing, China. PARTICIPANTS: Medical records and imaging data of children with traumatic SCI admitted to the rehabilitation research center from 2011 to 2020. INTERVENTIONS: Not applicable. OUTCOME MEASURES: Data on age, sex, cause of injury, neurological level of injury, impairment scale of SCI and details of spine fracture or dislocation were all collected and analyzed. RESULTS: A total of 351 patients were included in the study, including 133 males (37.9%) and 218 females (62.1%). There were 231 cases (65.8%) without spine fracture or dislocation. SCI without fracture or dislocation (SCIWORA) was the most common in children between the age of 5 and 14 years (77.9%), and injuries caused by sports were the most common in girls (90.8%). Among sports injuries, those due to a special dance movement called "Xia-Yao" in Chinese, which involves hyperextension of the trunk, constituted the majority, with the neurological level of injuries located predominantly in the middle (34.6%) and lower (44.2%) thoracic levels. CONCLUSION: Girls between the ages of 5 and 14 years constituted the majority of SCIWORA injuries at the thoracic levels, which were caused mainly by "Xia-Yao". Overall, careful attention should be paid to prevent this kind of injury in children.

Oscillating field stimulation promotes axon regeneration and locomotor recovery after spinal cord injury.

Oscillating field stimulation (OFS) is a potential method for treating spinal cord injury. Although it has been used in spinal cord injury (SCI) therapy in basic and clinical studies, its underlying mechanism and the correlation between its duration and nerve injury repair remain poorly understood. In this study, we established rat models of spinal cord contusion at T10 and then administered 12 weeks of OFS. The results revealed that effectively promotes the recovery of motor function required continuous OFS for more than 6 weeks. The underlying mechanism may be related to the effects of OFS on promoting axon regeneration, inhibiting astrocyte proliferation, and improving the linear arrangement of astrocytes. This study was approved by the Animal Experiments and Experimental Animal Welfare Committee of Capital Medical University (supplemental approval No. AEEI-2021-204) on July 26, 2021.

Efficacy of lumbar kinetic chain training for staged rehabilitation after percutaneous endoscopic lumbar discectomy.

BACKGROUND: Percutaneous endoscopic lumbar discectomy (PELD) is a promising minimally invasive treatment for lumbar disc herniation (LDH). Postoperative rehabilitation can improve patient outcomes. Not only rehabilitation for surgical trauma but also rehabilitation for lumbar spine and lower kinetic chain dysfunction should be performed. The aims of this study were to investigate the efficacy of a lumbar kinetic chain training for staged rehabilitation after PELD for LDH. METHODS: Fifty one LDH patients treated with PELD were studied. After surgery, patients underwent lumbar kinetic chain training for staged rehabilitation( staged group) or regular low back rehabilitation (regular group). The staged rehabilitation programme included three phases from 2 to 6, 7-12, and 13-24 weeks postoperatively, and different physical therapies were performed during these phases. The low back pain visual analogue scale (VAS), JOA score, ODI, SF-36, and cross-sectional area of the lumbar multifidus on MRI were assessed, and gait analysis was performed. RESULTS: Twenty five patients in staged group and twenty six patients in regular group were included. There were no significant differences in age or sex between the two groups at baseline (p > 0.05). The VAS score decreased and the JOA and SF-36 scores increased in both groups from baseline to 6 weeks (P < 0.05). In the staged group, compared with the regular group, the VAS and ODI scores were lower and the JOA and SF-36 scores were higher at 6 weeks (P < 0.05); the VAS and ODI scores were lower and the SF-36 score was higher at 12 weeks (P < 0.05); the SF-36 score was higher at 24 weeks (P < 0.05); the cross-sectional area of the lumbar multifidus showed no differences at 12 weeks (P > 0.05); and the left-right support ratio of gait was higher at 24 weeks (P < 0.05). CONCLUSIONS: The staged rehabilitation programme for LDH after PELD promoted postoperative recovery, and the efficacy of lumbar kinetic chain training was higher than that of regular low back muscle exercise.

Minimum Seven-Year Follow-Up Outcomes of Percutaneous Endoscopic Lumbar Discectomy for Lumbar Degenerative Disease.

PURPOSE: To investigate the long-term (> 7 years) clinical outcomes of percutaneous endoscopic lumbar discectomy for lumbar degenerative disease to address postoperative problems including postoperative dysesthesia (POD), residual back pain and segmental instability. METHODS: Inclusion and exclusion criteria were established. All patients who met the above criteria were treated by PELD using the transforaminal approach. Limited discectomy was performed to preserve the disc material in the intervertebral space as much as possible. The Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) score, visual analog scale (VAS) score for back pain (VAS-B) and leg pain (VAS-L) and Modified MacNab's criterion were used for clinical evaluation. Radiographic parameters including height of intervertebral disc and segmental instability were also evaluated. RESULTS: Forty-two patients (24 men and 18 women) who met our inclusion and exclusion criteria were included in our study. The average follow-up period was 95.71±5.63 months (ranging from 87 to 105 months). There were no neurological complications associated with the operation. POD was found in 14.29% of patients, while only 2 patients (4.76%) complained of mild dysesthesia at final follow-up. Two patients (4.76%) required revision surgery during the follow-up period. The final follow-up ODI, JOA score, VAS-B and VAS-L were significantly better than preoperative values. The average disc-height ratio was 84.52±5.66% of the preoperative disc height. No instability at the operation level was noted at final follow-up. CONCLUSION: Our study showed that PELD using the transforaminal approach can provide favorable results after a long-term follow-up period. POD is a common complication at initial prognosis. Limited discectomy can preserve the disc height well and minimize the risk of residual back pain.

Ischemic damage may play an important role in spinal cord injury during dancing.

STUDY DESIGN: Retrospective analysis. SETTING: China Rehabilitation Research Center, Beijing, China. OBJECTIVE: To explore possible mechanisms underlying spinal cord injury (SCI) in children caused by hyperextension of the spine while dancing. METHODS: The clinical records of 88 children with SCI (mean age, 5.97 years; age range, 4-10 years) admitted to our hospital from January 1989 to October 2019 were retrospectively reviewed. Computed tomography and magnetic resonance imaging were performed on the day of injury. The time from injury to development of paralysis, as well as post-injury activities were surveyed, while abnormal patterns on images, the range of the involved vertebrae, and the extents of edema and atrophy were assessed. RESULTS: Among the 88 patients, 6 (6.8%) were unable to move immediately after SCI, while paralysis occurred in 42, 23, and 17 patients at <30, 30-60, and >60 min after SCI, respectively. The neurological level of injury of 84 patients was between T4 and T12. On sagittal T2-weighted images (T2WIs), the longitudinal range of spinal cord edema was more than one vertebral body in 65 patients, while spinal cord atrophy below T8 was found in 40 patients. On axial T2WIs, although three patients had none, long T2 signals were found in the central gray matter of seven patients. Meanwhile, necrosis of the central area combined with the peripheral white matter was observed in 57 patients, while three patients had total involvement on a cross section. CONCLUSION: Ischemia-related damage, rather than direct trauma to the spinal cord, may play an important role in SCI due to spinal hyperextension during dancing.

Heterogeneity among traumatic spinal cord injuries at the thoracolumbar junction: helping select patients for clinical trials.

STUDY DESIGN: Retrospective analysis. SETTING: China Rehabilitation Research Center, Beijing, China. OBJECTIVE: A retrospective study that documents the modalities and clarifies the heterogeneity among spinal cord injuries (SCIs) caused by trauma to the thoracolumbar vertebral junction. METHODS: X-ray and MRI imaging, neurological records, and the urodynamics results of 190 patients were reviewed and used to categorize different SCI modalities. First, injuries were divided into complete and incomplete injuries using the International Standard for Neurological Classification of Spinal Cord Injury. Next, the complete injuries were further grouped using the neurological level of injury and Long T2 signal from mid-sagittal MRI images, whereas the bulboconvernosus reflexes were also used as a reference to detect injury to the sacral cord. RESULTS: The SCI modalities were classified into five categories: pure complete epiconus lesion with caudal cord intact (G1), complete epiconus injury with conus medullaris (CM) totally involved in the lesion (G2), CM syndrome, cauda equine syndrome without sacral sparing (G3 and G4), and incomplete injury (G5). CONCLUSIONS: The heterogeneity of SCIs at the thoracolumbar junction was documented, a criterion we propose to be of great significance when selecting patients for clinical trials. In particular, the G2 group, which comprises nearly one third of the patients with epiconus lesions, is sometimes mistaken as G1, an observation that has thus far received insufficient attention.

Compensation for injury potential by electrical stimulation after acute spinal cord injury in rat.

Injury potential, a direct current potential difference between normal section and the site of injury, is a significant index of spinal cord injury. However, its importance has been ignored in the studies of spinal cord electrophysiology and electrical stimulation (ES). In this paper, compensation for injury potential is used as a criterion to adjust the intensity of stimulation. Injury potential is modulated to slightly larger than 0 mV for 15, 30 and 45 minutes immediately after injury by placing the anodes at the site of injury and the cathodes at the rostral and caudal section. Injury potentials of all rats were recorded for statistical analysis. Results show that the injury potentials acquired after ES are higher than those measured from rats without stimulation and much lower than the initial amplitude. It is also observed that the stimulating voltage to keep injury potential be 0 remain the same. This phenomenon suggests that repair of membrane might occur during the period of stimulation. It is also suggested that a constant voltage stimulation can be applied to compensate for injury potential.

Electrical stimulation modulates injury potentials in rats after spinal cord injury.

An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This injury potential, as well as injury current, can be modulated by direct current field stimulation; however, the appropriate parameters of the electrical field are hard to define. In this paper, injury potential is used as a parameter to adjust the intensity of electrical stimulation. Injury potential could be modulated to slightly above 0 mV (as the anode-centered group) by placing the anodes at the site of the injured spinal cord and the cathodes at the rostral and caudal sections, or around -70 mV, which is resting membrane potential (as the cathode-centered group) by reversing the polarity of electrodes in the anode-centered group. In addition, rats receiving no electrical stimulation were used as the control group. Results showed that the absolute value of the injury potentials acquired after 30 minutes of electrical stimulation was higher than the control group rats and much lower than the initial absolute value, whether the anodes or the cathodes were placed at the site of injury. This phenomenon illustrates that by changing the polarity of the electrical field, electrical stimulation can effectively modulate the injury potentials in rats after spinal cord injury. This is also beneficial for the spontaneous repair of the cell membrane and the reduction of cation influx.

[Transferrin receptor imaging for tracing mesenchymal stem cells implanted in the spinal cord].

OBJECTIVE: To explore the feasibility of tracing mesenchymal stem cells in vivo with scintigraphy. METHODS: Transferrin receptor expression of cultured mesenchymal stem cells (hMSCs) was quantified with radioligand-receptor binding assay before the cells were transplanted into the spinal cord of rabbits. (131)I-labeled transferrin was then administered into the subarachnoid space of the rabbits, and scintigraphic images were acquired with a gamma camera at different time points after the administration. In the control experiments, (131)I-labeled human serum albumin was used in stead of (131)I-transferrin as the tracer, or only PBS was injected without stem cell transplantation. The images were semi-quantitatively analyzed with region of interest (ROI) techniques, and the phosphor imaging on the spinal sections were performed. RESULTS: Radioligand-receptor binding assay showed 10 770 binding sites with high affinity (KD=0.982 nmol/L) for Fe saturated transferrin on each human mesenchymal cell. Visible accumulation of radioactivity at the cell transplantation sites was observed 16 h and 24 h after intrathecal injection of (131)I-transferrin tracer, but not in two control groups. ROI analysis showed that the difference between (131)I-transferrin and the control groups was statistically significant (P<0.05). Phosphor imaging further verified that it was the specific coupling of transferrin to the implanted cells that resulted in radioactivity accumulation at the transplantation sites. CONCLUSIONS: Transferrin receptor imaging is capable of in vivo tracing of the implanted stem cells, and has the potential for use in non-invasive monitoring for stem cell transplantation therapy after further technical improvements.

[D2 receptor expression on immortalized human neural progenitor cell line hNPC-TERT in vitro and in vivo].

OBJECTIVE: To observe D(2) receptor expression on human neural progenitor cell line hNPC-TERT before and after transplantation into rabbit central nervous system. METHODS: D(2) receptor expression on cultured hNPC-TERT cells was verified and quantitatively analyzed with immunofluorescence assay and receptor radio ligand binding assay, respectively. 3 x 10(6) hNPC-TERT cells were implanted in the spinal cord of New Zealand rabbit with HeLa cells as the control. Two days after implantation, positron-emission tomography (PET) scan with (11)C-raclopride as the radiotracer was performed in the living animals or for the isolated spinal cords, and cryosections of the spinal cord containing the implanted cells were prepared for immunofluorescence assay. RESULTS: Cultured hNPC-TERT cells showed high expression of D(2) receptor (Bmax=8 x 10(4)). PET scans of the rabbits identified visible radioactive accumulations at the site where hNPC-TERT cells were implanted but not at the site of HeLa cell implantation. Region of interest analysis showed a significant difference between the two cells in the maximal standard uptake value at the cell implantation sites. The results were further confirmed with ex vivo PET imaging of the spinal cord and tissue immunofluorescence assay. CONCLUSION: Human neural progenitor cells hNPC-TERT highly express dopamine D(2) receptors and retain this capacity after implantation into the spinal cord, suggesting their potential for treatment of such nerve system disease as Parkinson syndrome.

[Tracking neural progenitor cells transplanted into rabbit spinal cord by detection of dopamine receptor 2 with positron emission computed tomography].

OBJECTIVE: To explore the effect of in vivo positron emission computed tomography (PET) in tracking the stem cells transplanted into spinal cord. METHODS: Telomerase-immortalized human neural progenitor cells of the line hNPC-TERT were cultured. HeLa cells were used as control cells. RT-PCR was used to detect the mRNA expression of dopamine receptor 2 (D(2)) in both cell lines. (3)H-raclopride was added into the suspensions of these 2 cell lines. RT-PCR was used to detect the mRNA expression of D(2), and immunofluorescent staining was conducted on the cells to detect the protein expression of D(2). Twenty-two New Zealand rabbits were randomly divided into 4 groups to undergo transplantation of hNPC-TERT cell suspension into the spinal cord at the segment T10, or transplantation of HeLa cells. Two day after the transplantation some rabbits were killed to take out the spinal cord at the segment T10 to undergo immunofluorescent staining to examine the radioactivity in the spinal cord. Some rabbits were injected with (11)C-raclopride intravenously and then underwent PET imaging. RESULTS: RT-PCR showed that mRNA expression was positive in the hNPC-TERT cells but negative in the HeLa cells, and immunofluorescent staining showed protein expression of D(2) in the in the hNPC-TERT cells and not in the HeLa cells. The spinal cords specimens taken 2 days after transplantation had human-specific nuclear (HN) antigen positive and D(2) positive cells. Fluorescent microscopy showed that the hNPC-TERT cells in the injection site did not migrate remarkably; and showed that the D(2) staining was negative and HN antigen was positive in the HeLa cells. (11)C-raclopride PET imaging of the live rabbits showed accumulation of radioactivity at the hNPC-TERT cell injection site with a standard uptake value significantly higher than that of the HeLa cell transplantation group (P < 0.01). (11)C-raclopride PET imaging of the isolated spinal cords showed rounded focal image of increased radioactivity in the hNPC-TERT cell transplantation group and linear image of radioactivity without clear border in the HeLa cell transplantation group. CONCLUSION: PET imaging with as radiotracer targeting at specific cellular marker is effective in tracking cells into the body and in vivo visual evaluation of stem cell transplantation.

Effect of human neural progenitor cells on injured spinal cord.

OBJECTIVE: To study whether human neural progenitor cells can differentiate into neural cells in vivo and improve the recovery of injured spinal cord in rats. METHODS: Human neural progenitor cells were transplanted into the injured spinal cord and the functional recovery of the rats with spinal cord contusion injury was evaluated with Basso-Beattie-Bresnahan (BBB) locomotor scale and motor evoked potentials. Additionally, the differentiation of human neural progenitor cells was shown by immunocytochemistry. RESULTS: Human neural progenitor cells developed into functional cells in the injured spinal cord and improved the recovery of injured spinal cord in both locomotor scores and electrophysiological parameters in rats. CONCLUSIONS: Human neural progenitor cells can treat injured spinal cord, which may provide a new cell source for research of clinical application.

[In vitro study of combination rhOPG-Fc and alendronate on inhibition osteoclast].

OBJECTIVE: To study the effect of combination rhOPG-Fc and alendronate on mature osteoclasts. METHODS: Recombinant human osteoprotegerin secretory expression in P. pastoris was performed. Osteoblasts were got from new born mouse skeletal bone and proved by ALP staining and incubated together with osteoclasts precursor cell line Raw 264.7 in 96 well plate. After 9 d, 10 micromol/L ALN, 10(-5) g/L rhOPG-Fc, 10 micromol/L ALN + 10(-5) g/L rhOPG-Fc, 5 micromol/L ALN + 5 x 10(-6) g/L rhOPG-Fc were added to these coculture systems. Osteoblasts cultured without the drugs mentioned above served as controls. TRAP stain positive cells counting and cortical bone pit formation counting were preformed in the following the 3rd and 7th d. RESULTS: SDS-PAGE and Western blot showed that molecular weight of the expressed protein was about 55 KD, and it could reach specifically with anti-IgG antibody. Many multi-nuclear TRAP stain positive cells were found in the coculture control group after 9 d incubation, and proved to be mature osteoclasts by TRAP stain. In the 3rd and 7th d after the addition of rhOPG-Fc, ALN or both, TRAP stain positive cells counting and cortical bone pit formation counting decreased significantly in the rhOPG-Fc, ALN or both groups than in the control group, and the combine group (10(-5) g/L rhOPG-Fc + 10 micromol/L ALN) decreased most significantly when compared with rhopG-FC or ALN single. CONCLUSIONS: rhOPG-Fc can decrease the number of osteoclasts and inhibit their function. The combination of both rhOPG-Fc and ALN shows the significant inhibition effect on mature osteoclasts.

In vivo tracking of implanted stem cells using radio-labeled transferrin scintigraphy.

The possibility of monitoring stem cells in vivo with radionuclide imaging after transplantation was investigated. Based on the results of a radioligand receptors assay that human mesenchymal stem cells (hMSCs) express a high level of transferrin receptors, iodinated transferrin (131I-Tf(Fe)2) was chosen as the radiotracer for imaging the cells implanted into the spinal cords of rabbits. Accumulation of radioactivity at the cell transplanted sites was assessed 16 and 24 hours post-intrathecal injection of 131I-Tf(Fe)2. Transferrin receptors expression and Tf binding of the implanted cells were verified by immunofluorescence and ex vivo phosphor imaging. The specificity of Tf uptake of hMSCs was proved through control experiments, i.e., replacing 131I-Tf(Fe)2 with 131I labeled human serum albumin as the tracer or substituting hMSCs with phosphate buffered saline as the grafts. Despite some defects, such as the invasive administration of the tracer and the non-specificity of transferrin receptors as a marker of stem cells in this preliminary study, the technique of nuclear medicine imaging is considered to have great potential in tracking implanted cells in vivo.

[Transferrin receptor expression of human mesenchymal stem cells and in vitro tracking by autoradiography after transplantation in spinal cord].

OBJECTIVE: To determine transferrin receptor (TfR) expression of human mesenchymal stem cells (MSCs) in vitro and after transplantation in rabbit spinal cord,and to detect implanted MSCs by in vitro autoradiography. METHODS: Human mesenchymal stem cells (hMSCs) were isolated from fetal blood. Flow cytometry assay, immuno-fluorescent staining and receptor binding assay were used to determine TfR expression of hMSCs. Radioiodinated transferrin saturated with iron [(125)I-Tf(Fe)(2)] was used as tracer. The hMSCs transplanted in rabbit spinal cord was tracked by in vitro autoradiography. Diffusion of (125)I-Tf(Fe)(2) in spinal cord was examined with autoradiography. RESULTS: TfR expression of MSCs was demonstrated by flow cytometry assay, immuno-fluorescent staining and receptor binding assay in vitro. (125)I-Tf(Fe)(2) bound to hMSCs with a equilibrium dissociation constant (KD) of (0.98+/-0.12) nmol/L and a maximal density of binding sites (B(max)) of (107 702+/-6 226) sites per cell. Immuno-fluorescent staining showed that TfRs were expressed on hMSCs on the 2nd day but not be expressed on the 10th day post transplantation. Autoradiography showed distinct accumulation of (125)I-Tf(Fe)(2) but not (125)I-HSA at hMSCs implantation sites of spinal cord sections on the 2nd day post transplantation. (125)I-Tf(Fe)(2) had diffused into spinal cord 16 hours after incubation. CONCLUSION: Implanted hMSCs could be detected by in vitro autoradiography with (125)I-Tf(Fe)(2) on the 2nd day after being transplanted in spinal cord. To track implanted hMSCs with radionuclide imaging techniques in vivo, TfR was a suitable target for imaging and radioiodinated Tf(Fe)(2) was a feasible tracer.

Radionuclide imaging of mesenchymal stem cells transplanted into spinal cord.

In vivo tracking of stem cells implanted to spinal cord by radionuclide imaging was investigated. The high expression of transferrin receptor on human mesenchymal stem cells (hMSCs) was verified by flow cytometry, radioligand binding and immunofluorescence. Radiolabelled transferrin was chosen as a tracer for scintigraphic imaging of the hMSCs transplanted into spinal cord of rabbits. Comparative experiments with radiolabelled human serum albumin as tracer and PBS as graft as well as ex vivo autoradiography demonstrated the specific uptake of radiolabelled transferrin of hMSCs. hMSCs could be detected in vivo with radiolabelled transferrin targeting at cellular transferrin receptors at an early stage after transplantation into spinal cord.