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@#ObjectiveTo explore the feasibility and potential benefit of olfactory ensheathing cell (OEC) intraspinal transplantation in the treatment of intractable chronic neuropathic pain after spinal cord injury (SCI).Methods17 patients, 15 male and 2 female, with intractable chronic neuropathic pain after spinal cord injury was treated by OEC implant from November, 2004 to November, 2007. The age ranged from 18 to 68 (mean 40.4) years. The etiology of cord impairment included car accidents, falls, radiation damage, machine extrusion, gun-shot, and diving. The patients suffered severe persistent pain for 6 to 309 (mean 102.2) months, and the time points when cell therapy were administrated in the patients ranged from 6 to 312 (mean 105.9 months) after their injuries. Olfactory bulbs were harvested and trypsinized down to single fetal OECs. They were cultured for 12～14 days before implant. The fetal OECs were transplanted by injection into spinal cord at opposing ends of the injury site. The degree of pain was assessed and compared before operation and long-term follow-up according to the International Association of Neurorestoratology Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS), i.e., 0 point means extreme pain, uncontrolled; 1 point, severe pain, narcotics required; 2 points, mild pain, ordinary pain killer effective; 3 points, no pain.ResultsThe follow-up and pain reevaluation were performed at 0.5 to 88 months with an average of 17.5 months after cell transplantation. The mean score of pain amelioration is 1.2 points.ConclusionThe OEC intraspinal transplantation appears to have a promising role in treatment of intractable chronic neuropathic pain after SCI.
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@#A variety kinds of cells were transplanted for brain and spinal cord repair, and some types of cells have been used for stroke, which including bone marrow stromal cells, neural stem/progenitor cells, olfactory ensheathing cells, human neuronal cell and so on. The complementary advantages of different types of cells and the integrated application of varied strategies of nerve restoration is an important direction for future exploration.
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Objective To compare the image quality and scanning dose of time-subtraction and dual-energy-subtraction cerebral CT angiography, and to assess clinical application value of both methods. Methods Plain and enhanced scanning were performed on 60 patients suspected cerebral vessel diseases with dual-source CT. Dual-energy mode with tube voltages of 140 and 80 kV was used in enhanced scanning, and data of two different energy were collected in one scanning. ①Traditional removed-bone digital subtraction (time-subtraction) with plain and 80 kV enhanced scanning data were obtained. Volume render (VR) and maximum intensity projection (MIP) reconstruction were finished; ②Direct removed-bone digital subtraction (dual-energy subtraction) with 80 kV and 140 kV enhanced scanning data were obtained. VR and MIP reconstruction were finished. The image quality of VR and MIP was divided into 4 grades, and were compared as well as average effective radiological dose. All the diseases were confirmed with surgery or DSA. Average effective radiological dose was compared with time-subtraction and dual-energy subtraction. Results Internal carotid artery trunk and branch and Willis circles were displayed clearly with two methods in 60 cases. No significant difference was found (P>0.05) between total quality score of the two methods. The size, shape, neck and axis point of aneurysm in 24 cases were clearly displayed, so as the shape and extent of abnormal vessel bolus in 4 cases, while arteries and veins were also clear in artery-vein malformation; ③The average radiological dose was (26.60±0.50)mSv in time-subtraction and (22.40±0.50) mSv in dual-energy subtraction. Conclusion The normal, abnormal vessels and diseases can be clearly displayed at time-subtraction and dual-energy subtraction CTA. The effect of dual-energy-subtraction is better than that of time-subtraction CTA in no-cooperation patients, and the radiological dose is lower in dual-energy CTA.
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Totally 1 patient were selected from Beijing Xishan Institute for Neuroregeneration and Functional Recovery in Shijingshan District in May 2006. The patient received acupuncture treatment in trideca-ghost points after olfactory ensheathing cells (OECs) transplantation. Detailed acupuncture method and acupuncture point were as follows: Acupuncture was performed from left side on Shuigou (DU 26), Jiache (ST 6), Fengfu (DU 16), Chengjiang (RN 24), Shangxing (DU 23), oblique needling from Shuigou to mittele muschel 0.3 cun. Needle insertion on Chengjiang was from left to right, for 1 minute without retaining needle. Then acupuncture on Shaoshang (LU 11), Daling (PC 7), Jianshi (PC 5), Quchi (LI 11) of both sides, and lower limbs: Yinbai (SP 1) and Shenmai (BL 62) was conducted. Acupuncture on Jiache and Quchi was retained until the patient vellicated limbs. Punctured on Dicang (ST 4) if the patient had spasm on angulus oris, about 20 minutes every time, once a day. After the treatment, the patient had some improvements in the consciousness and electrophysiology. Significant pain reaction appeared, and the endings of extremities had some little movement. The patient could turn head and twist shoulder. Evoked potential in electromyogram (EMG) had certain amelioration.
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To cure one patient with spinal cord injury (SCI), who hospitalized for both legs couldn't moving for 21 years after external injury, by using the olfactory ensheathing cells (OECs) transplant and acupuncture treatment. The patient was diagnosed as ischemic SCI (below the T11) according to the neurological test and MRI for dorsal vertebra. T11 spinous process was made to be the center mark through operation with the length of about 3 cm. The area between the atrophique spinal cord and normal spinal cord without vessel was selected and injected with OECs 0.5?109 L-1. Hemostasis, stitching, binging and fixation were performed respectively, and normal treatment was given by using antibiotics. At 14 days after operation, the temperature on skin increased a little, and acupuncture treatment and rehabilitation therapy were performed. The acupoints were as following: Baihui (DU21), Yintang (EX-HN3), Hegu (LI4), Zhongji (RN3), Guanyuan (RN4), Biguan (ST31), Fengshi (GB31), Futu (ST32), Dubi (EX-LE5), Zusanli (ST36), Xuehai (SP10), Yinlingquan (SP9), Sanyinjiao (SP6), Jiexi (ST41), Taixi (KI3), Fuliu (KI7), Taichong (LR3), and Shenmai (BL62). The treatment was given by mild reinforcing and attenuating with 30-minute retention. The rehabilitation: The needle pressing, manipulation for muscular atrophy, bicycle practicing, andimperative standing were performed. After 2 weeks, the skin temperature of the patient increased with obvious improvement in his right leg. The physical strength of the patient was reinforced with less perspiration, and the patient could walk 3 km without fatigue, which indicated that after OECs transplant, treatment with acupuncture, massage and other rehabilitation trainings could facilitated the improvement of SCI of the advance stage as well as the amelioration of muscular atrophy.
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Objective To evaluate proton MR spectroscopy (1H-MRS) for detection of the motor cortex and adjacent brain in amyotrophic lateral sclerosis (ALS) patients with apparent upper motor neuron involvement after olfactory ensheathing cells(OECs) transplantation. Methods From December 2004 to February 2005, 7 patients with clinically definite ALS who could safely undergo MRS were admitted into the perspective study. The neurological status, ALS functional rating scale (ALSFRS), EMG, and 1H-MRS taken before and 2 weeks after operations were carefully analyzed. The NAA/Cr and Cho/Cr ratios were measured in the cerebral peduncle, genu and posterior limb of the internal capsule, corona radiata and precentral gyrus. Results The ALSFRS in 2 cases improved obviously whose ALSFRS increased from 30 to 33 and from 29 to 34 respectively. And 5 cases remained stable 2 weeks after OECs transplantation. Statistical analyses for all seven cases showed both the NAA/Cr and Cho/Cr ratios decreased, but in the two cases with ALSFRS improvement the NAA/Cr increased in the certain anatomic position which confirmed the neurological and EMG findings. Conclusion The proton MR spectroscopy is a suitable noninvasive measure for ALS evaluation. The preliminary study suggests that two of the seven ALS cases improved apparently short-term after OECs transplantation. More patients are required for the clinical study and longer follow-up duration is needed for future research.
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In order to control the quality of all parts of the process for culturing,preparing and using clinically the human embryo olfactory ensheathing cells (OECs),the conduct standard of culturing human OECs from olfactory bulb is formulated. Because the strict conduct process can reduce the human factor as much as possible and ensure the stability of the cell quality. Therefore,during the culturing process of human embryo OECs, as for the embryo sample of OECs from olfactory bulb,the standard of lab condition and cell culture must be set strictly. The key steps of conduct process must be regulated,the freezing and resuscitating process of OECs must be controlled,the test method for microbial contamination during cell culture must be proposed and the risk must be reduced,then the quality of the human OECs from olfactory bulb can be guaranteed during the clinical application.
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ObjectiveTo determine whether transplanting olfactory ensheathing cells(OECs)is effective in controlling or re.versing the deterioration caused by amyotrophic lateral sclerosis(AtS). MethodsUetwcen February 2003 and April 2006,327 pa-fients(241 males and 86 females)with probable or definite ALS(diagnosed according to the El Escorial criteria)received dle oECstransplantation.Their ages ranged from 20 to 84 years(51.6±11.1 years).The duaration of sympltoms before surgical trealment wit84.8months to 13 years(2.9±2.0 years).OECs were cultured and.injected into palllological regions of the spinal cord and/or bilateralcoroila radiata of the brain;the patients were divided into three groups,group A(cord only,n=29),group B(cord and brain,,n=6),and group C(brain only,n=292)based on the transplant sites.ResultsThe patient's neurological function was assessedboth before and at4 weeks after transplantation by using the Amyolrophic Lateral Sclerosis Functional Rating Scale(ALSFRS)of the ALSCNTF Trealment Study(ACTS).The$cores were increased from 17.2±8.6 pre-operation to 20.1±9.7 post-operation in group A(P<0.05),from 24.2 4-6.8 to 25.7±6.6(P>0.05)in group B,and from 20.3±8.6 to 22.0±9.4(P<0.001)in group C.There were no significant difference inincreased ALSFRS scores amongthe three groups(P>O.05).The total improvement rate of neurological function was 77.1%(252/327).The result of electramyographic examination showed that spontaneous potential diminishedand/or disappeared,the amplitude of the motor unit action potential decreased remarkably andthe numbers of motor unitaction potentialgreatly increased in 261 cases(79.8%).Sixteen patients(4.9%)experienced the various complications including headache.short-term fever,seizure attack,central nerve system infection,pneumonia,respiratory failure,urinary tract infection,heartfailure,and pos-sible pulmonary embolism;of them,there were 4 deaths(1.2%). ConclusionThese preliminary results suggest that the OECs trasplantafion is effective in controlling or reversing the physiological deterioration caused by ALS.
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BACKGROUND: It was thought that there was no regeneration capacityin central nerves. Recent research shows that regeneration capacity of injured neural axons and recovery of some neurological functions can be achieved by changing local surroundings after spinal cord injury (SCI).OBJECTIVE: To probe into whether the transplantation of fetal olfactory ensheathing cells (OECs) in recovering the neurological functions of patients with chronic SCI is safe, feasible, and effective.DESIGN: Auto-control observation before and after surgery.SETTING: Neurological Research and Treatment Center of Beijing Xishan Hospital; Second Department of Neurosurgery in Beijing Chaoyang Hospital Affiliated to Capital University of Medical Sciences; Second Department of Neurosurgery in Naval General Hospital.PARTICIPANTS: A total of 171 patients with chronic spinal cord injury were selected from the Second Department of Neurosurgery in Beijing Chaoyang Hospital Affiliated to Capital University of Medical Sciences and the Second Department of Neurosurgery in Naval General Hospital betweenNovember 2001 and February 2003, of which there are 147 patients with complete injury and 24 ones with incomplete injury. Post-injury period ranged from 0.5 to 18 years. Process of treatment is discussed and permitted by relevant Medical Ethics Committees. Cells were obtained from voluntary donors and patients agreed to receive the treatment.METHODS: ① Fetal olfactory bulbs were cultured for 12-17 days after being digested into single cells. ② Fetal OECs were transplanted into sites rostral and caudal to the epienter. ③ Neurological functions of all patients 2-8 weeks before and after operation were evaluated according to the scoring standard of ASIA.MAIN OUTCOME MEASURES: ① Status of functional recovery in spinal cord of patients after transplantation of OECs. ② Harmful events and side effects.RESULTS: A total of 171 patients were involved in the analysis of results.①Status of functional recovery in spinal cord of patients with OECs transplantation: Partial neurological functions of 171 patients rapidly recovered,whose motor function score increased from (34.5±20.3) points before operation to (42.0±20.0) points (P ＜ 0.001) after operation, score of light touch increased from (47.2±24.0) points to (61.8±23.0) points (P ＜ 0.001) after operation,score of pain sense increased from (48.6±23.5) points to (64.0±22.8) points (P ＜ 0.001). ②Harmful events and side-effects: Early manifestations of spinal cord injury induced by infection in surgical area of one patient aggravated; two patients suffered from serious pulmonary infection,one patient from thalamic hemorrhage. Three patients mentioned above died of serious respiration and circulatory failures.CONCLUSION: OEC transplantation can rapidly promote partial neurological function of patients with chronic SCI, while the mechanism needs further observing.
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Objective To explore the influence factors for the functional improvement after the fetal olfactory ensheathing cell (OEC) transplantation for chronic spinal cord injury(SCI). Methods The olfactory bulbs were harvested and trypsinized down to single fetal OEC. They were cultured for 12-17 days prepared for use. From November 2001 to December 2003, a total of 300 patients volunteered for the fetal OEC transplantation, among whom 222 suffered from complete chronic SCI and 78 suffered from incomplete chronic SCI. The procedures were performed on the patients with a disease course ranging from 6 months to 31 years (average 3.1 years) after their injuries. The fetal OEC was transplanted by the form of injections into the spinal cord at the upper and lower ends of the injury site. All the patients were assessed by the ASIA standard before the transplantation and 2-8 weeks after the transplantation. The influence factors including age, sex, duration after the injury, and injury degrees and levels were compared with those in the functional improvement after fetal OEC transplantation. Results The partially-improved neurological functions assessed by the ASIA standard were indicated by the motor scores increasing from 39.1±20.6 to 45.9±20.3 (P<0.001), the light touch scores from 51.7±24.9 to 63.4±23.0 (P<0.001), and the pin prick scores from 53.0±24.2 to 65.3±22.7(P<0.001). There was no significant difference in the functional improvement of the motor, light touch, and pin brick when compared with the age, sex, duration after the injury, and the injury degrees and levels. The motor scores and light touch scores at the cervical level were higher than the scores at the thoracic level. Conclusion The fetal OEC transplantation can partially improve the neurological functions quickly in treatment of the chronic spinal cord injury. All the influence factors except the motor scores and light touch scores, which were higher at the cervical level than at thoracic level, have no impact on the functional improvement after the fetal OEC transplantation.
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Objective To determine the safety of the fetal olfactory ensheathing cell(OEC) transplantation in patients with chronic spinal cord injury (SCI) by examination of the magnetic resonance imaging (MRI). Methods A prospective clinical study involving 16 patients with chronic SCI was designed to investigate the feasibility and biological safety of the fetal OEC transplantation in treatment of SCI. The olfactory bulbs from the 3-4-month-old aborted human fetuses following the strict ethical guidelines were harvested and trypsinized down to single fetal OEC. These cells were then cultured for 12-17 days and were prepared for a clinical use. From November 2001 to December 2002, 16 patients with chronic SCI were randomly enrolled. The patients suffered from SCI for 1.5-8 years (average 4.3 years) after the injury. The suspension (50 μl) containing about 1×106 fetal OECs was transplanted by an injection into the patients' spinal cords above and below the injury site. All the patients were assessed before the transplantation and were followed up with MRI for 29-42 months (average 38 mon) after the transplantation. Results No cell-related adverse effects were observed in any patient during the follow-up period. The follow-up with MRI did not reveal any development of optic glial tumor, tumor-like mass, new hemorrhage, edema, expanding cyst, new cyst formation, infection or disruption of the neural structure in the transplant site of all the patients. Conclusion This is the first clinical study demonstrating the long-term safety of the OEC therapy for SCI. The results indicate that our protocol is feasible and safe in treatment of patients with chronic SCI within 38 months after the injury. Although the size of the samples for our study was not big enough, the positive results of the study have encouraged us to make a further research in this field.
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<p><b>OBJECTIVE</b>To evaluate the restoration of function after spinal cord injury (SCI) in patients of different ages who have underwent intraspinal transplantation of olfactory ensheathing cells (OECs).</p><p><b>METHODS</b>One hundred and seventy-one SCI patients were included in this study. Of them, 139 were male and 32 were female, with age ranging from 2 to 64 years (mean, 34.9 years). In all SCI patients the lesions were injected at the time of operation with OECs. According to their ages, the patients were divided into 5 groups: </= 20 years group (n = 9), 21 - 30 years group (n = 54), 31 - 40 years group (n = 60), 41 - 50 years group (n = 34) and > 51 years group (n = 14). The spinal cord function was assessed based on the American Spinal Injury Association (ASIA) Classification System before and 2 - 8 weeks after OECs transplantation. One-way ANOVA and q test were used for statistical analysis, and the data were expressed as mean +/- SD.</p><p><b>RESULTS</b>After surgery, the motor scores increased by 5.2 +/- 4.8, 8.6 +/- 8.0, 8.3 +/- 8.8, 5.7 +/- 7.3 and 8.2 +/- 7.6 in 5 age groups respectively (F = 1.009, P = 0.404); light touch scores increased by 13.9 +/- 8.1, 15.5 +/- 14.3, 12.0 +/- 14.4, 14.1 +/- 18.5 and 24.8 +/- 25.3 respectively (F = 1.837, P = 0.124); and pin prick scores increased by 11.1 +/- 7.9, 17.2 +/- 14.3, 13.2 +/- 11.8, 13.6 +/- 13.9 and 25.4 +/- 24.3 respectively (F = 2.651, P = 0.035). Restoration of pin prick in > 51 years group was better than other age groups except 21 - 30 years group.</p><p><b>CONCLUSION</b>OECs transplantation can improve the neurological function of spinal cord of SCI patients regardless of their ages. Further research into the long-term outcomes of the treatment will be required.</p>