尿动力学检查对干细胞移植治疗脊髓损伤后排尿障碍的临床疗效评估

目的 探讨通过尿动力学检查判断间充质干细胞移植治疗脊髓损伤后排尿障碍的临床疗效.方法 对20例胸10-腰1段脊髓损伤后遗症患者行脐带间充质干细胞移植,并进行术前和术后半年尿动力检查,ASIA损伤分级评分.结果 60％患者尿道括约肌功能、膀胱顺应性明显改善.结论 间充质干细胞移植可以显著改善胸腰段脊髓损伤后遗症患者排尿障碍,恢复尿道括约肌和膀胱功能,提高患者生活质量.     

自体分选造血干细胞和异体脐带间充质干细胞移植治疗神经系统变性疾病

背景：将自体分选造血干细胞和异体脐带间充质干细胞技术应用于临床,试图寻找一种新的治疗神经系统变性疾病的可行方法。 目的：探讨自体分选CD34+造血干细胞和异体脐带间充质干细胞治疗神经系统变性病的可行性。 方法：入选神经系统变性病患者21例,其中运动神经元病15例,脊髓小脑共济失调6例。取4 mL的脐带间充质干细胞或自体分选干细胞液经腰穿注射到患者蛛网膜下腔,每次注射的细胞数1.0×107。于干细胞治疗后3个月进行评分。 结果与结论：15例运动神经元病患者,治疗总有效率为80%,治疗前后的脊髓侧索硬化功能分级量表和自我评估问卷评分差异有显著性意义(P < 0.05);6例脊髓小脑共济失调患者,按ICARS评分,4例病情等级下降,治疗总有效率为77%。21例中4例有轻度低颅压性头痛(腰穿后),14例采用脐带间充质干细胞治疗的患者中2例在治疗后2 h出现短暂发热,其余患者治疗后未见明显不良反应。结果初步表明自体分选造血干细胞和异体脐带间充质干细胞治疗神经系统变性病临床疗效肯定,安全可行。     

移植人脐带间充质干细胞修复大鼠脊髓损伤

背景：已知人脐带间充质干细胞对脊髓损伤存在着潜在的治疗价值,然而,当前对移植人脐带间充质干细胞治疗脊髓损伤及机制方面研究很少。 目的：观察人脐带间充质干细胞对脊髓损伤大鼠的治疗效果。 方法：40只Wistar大鼠建立脊髓损伤模型,38只造模成功后随机摸球法分为3组：空白对照组：只接受单纯损伤,不做任何移植;DMEM移植组：损伤后1周予以5 μL DMEM局部移植;细胞移植组：损伤后1周予以5 μL准备好的人脐带间充质干细胞局部移植(细胞数1×106)。移植后对实验动物通过BBB评分、体感诱发电位与运动诱发电位观察后肢功能恢复情况。分别于损伤后2,4,6,8,10周随机于细胞移植组抽取大鼠2只,免疫组织化学染色观察人脐带间充质干细胞存活、迁移、分化,通过胶质纤维酸性蛋白阳性细胞染色比较各组损伤局部胶质瘢痕形成面积。 结果与结论：BBB评分损伤后4周细胞移植组高于其他两组(P < 0.05),损伤后12周细胞移植组与其他两组相比SEP、MEP潜伏期缩短、波幅值增高(P < 0.05)。免疫组织化学染色示人脐带间充质干细胞可向神经元、星形胶质细胞和少突胶质细胞分化,分化的少突胶质细胞并包绕轴突形成髓鞘。细胞移植组损伤局部胶质瘢痕面积均小于其他两组(P < 0.05),空白对照组、DMEM移植组间差异无显著性(P > 0.05)。提示未经体外诱导的人脐带间充质干细胞可于损伤大鼠脊髓体内向神经元、星形胶质细胞、少突胶质细胞分化,减小胶质瘢痕,并促进脊髓损伤大鼠神经功能的恢复。     

骨髓间充质干细胞修复损伤脊髓的实验及临床应用短期随访

背景：骨髓间充质干细胞治疗脊髓损伤的研究已经逐渐由动物实验过渡到临床,但其作用机制还不完全清楚。 目的：观察骨髓间充质干细胞移植对脊髓损伤大鼠脊髓功能的修复作用,并通过临床应用观察短期疗效。 方法：采用改良Allen's打击法造成Wistar大鼠脊髓损伤模型,将体外分离培养的骨髓间充质干细胞分别经尾静脉及损伤局部移植,应用改良Tarlov评分评定大鼠行为学变化,在光镜下对损伤脊髓病理切片进行对比分析。对5例脊髓损伤患者通过损伤原位注射、腰穿、静脉输注的方式行人自体骨髓间充质干细胞移植,并行神经功能及生活能力评定。 结果与结论：治疗后15 d,骨髓间充质干细胞尾静脉及损伤局部移植组大鼠运动功能评分较模型对照组显著提高;移植后7,15,30 d,脊髓病理切片显示骨髓间充质干细胞尾静脉及损伤局部移植组大鼠较模型对照组有显著恢复。临床患者骨髓间充质干细胞移植后半年神经功能及生活能力均有改善。     

脐带源与骨髓源干细胞移植治疗大鼠脊髓损伤的疗效比较

目的 观察人脐带间充质干细胞(HUCMSCs)与大鼠骨髓间充质干细胞(BMSCs)移植治疗大鼠脊髓损伤后的功能恢复和急慢性排斥反应.方法 选取SD大鼠40只按随机数字表随机分成3组:脐带间充质干细胞移植组16只、骨髓间充质干细胞移植组16只和PBS组8只.采用脊髓半切手术制作大鼠脊髓损伤模型,损伤后对脐带间充质干细胞移植组进行HUCMSCs移植,对骨髓间充质干细胞移植组行大鼠BMSCs移植,对PBS组移植同等剂量的PBS.通过BBB评分对各组动物的术后恢复进行评估比较.用ELISA法测定移植后3组动物不同时间点(移植后1周、1个月、2个月及3个月)血中IL-2及IL-10的水平,并通过免疫组化的方法检测移植局部病理切片CD3+细胞浸润的情况.结果 在移植后1周、1个月、2个月及3个月时,检测到干细胞移植组各个时间点大鼠静脉血中IL-2水平较PBS组明显升高,而IL-10水平较PBS组明显下降,差异均有统计学意义(P＜0.05).大鼠骨髓间充质干细胞移植组在移植后1周、1个月、2个月及3个月时大鼠静脉血中IL-2水平较脐带间充质干细胞移植组明显升高,IL-10水平较对照组明显下降,差异均有统计学意义(P＜0.05).三组在急性期(细胞移植后l周)移植局部均有大量CD3+细胞浸润.而移植的慢性期(细胞移植后3个月)大鼠骨髓间充质干细胞移植组仍存在大量CD3+细胞浸润,与其他两组相比差异均有统计学意义(P＜0.05).结论 异体干细胞细胞移植后可发生急、慢性免疫排斥反应.HUCMSCs较大鼠BMSCs有更低的免疫源性,更利于脊髓损伤的功能恢复.     

脐带间充质干细胞移植治疗终末期肝硬化的疗效及安全性

背景：骨髓间充质干细胞移植已应用于治疗终末期肝病并取得一定疗效。 目的：观察脐带间充质干细胞治疗终末期肝硬化患者的疗效及安全性。 方法：无菌条件下分离培养脐带间充质干细胞,选择60例肝硬化患者,在内科治疗基础上经肝动脉插管进行脐带间充质干细胞移植。 结果与结论：移植2,4,8,12周后,患者血清白蛋白、前白蛋白水平逐渐升高(P < 0.05),总胆红素、凝血酶原时间明显低于治疗前水平(P < 0.05)。移植后患者乏力、腹胀、纳差明显好转,未发生与移植相关的严重并发症。说明脐带间充质干细胞治疗终末期肝硬化安全有效,能改善患者的肝功能、凝血功能及临床症状。     

自体骨髓干细胞移植治疗慢性脊髓损伤28例分析

目的 观察自体骨髓干细胞移植治疗慢性脊髓损伤患者的临床疗效及安全性。方法 选择2010-01—2012-07江西省人民医院神经内科收治的慢性脊髓损伤患者28例,骨髓干细胞动员后,采自体骨髓干细胞进行鞘内注射移植治疗,骨髓干细胞数量(1.0~10.0)×107,1次/周,共治疗2次。分别于移植前和移植后1、3、12个月采用美国脊髓损伤学会(ASIA2000)制订的评分标准和改良的Barthel指数(MBI)评估疗效,并观察患者的不良反应。结果 MSCs移植1个月后,针刺痛觉评分、轻触觉评分、运动评分和MBI评分与入院时比较均明显改善(均P<0.05);移植3、12个月后各项评分与入院时比较均有显著差异(均P<0.01)。其中8例低热和3例低颅压性头痛,处理后症状完全消失。结论 自体MSCs移植治疗SCI可改善患者的运动和感觉功能,提高日常生活能力,且不良反应轻微。     

人脐带间充质干细胞移植治疗大鼠创伤性脑损伤

背景：脐带间充质干细胞体内移植治疗脑损伤的效果目前尚较少见报道。 目的：观察人脐带间充质干细胞移植对大鼠液压冲击脑损伤的治疗作用。 方法：从新生儿脐带中分离、培养间充质干细胞。制作中度打击大鼠脑损伤模型。实验分为4组：①脐带间充质干细胞移植组：损伤后原位移植脐带间充质干细胞。②对照组：损伤后原位注射等量DMEN/F12培养基。③单纯损伤组：仅施行损伤。④假损伤组：仅切开头皮及颅骨,不实施机械性损伤。 结果与结论：脐带间充质干细胞移植后1~3周,动物神经功能评分较对照组明显改善;4周后,各组动物神经功能评分均恢复正常。免疫组织化学检测表明少部分移植细胞表达神经元特异性烯醇化酶,胶质纤维酸性蛋白。与对照组相比,移植组损伤区血管内皮生长因子表达明显增加,凋亡细胞减少。提示脐带充间质干细胞脑内移植有助于促进创伤性脑损伤后的早期功能恢复,这种治疗效果是通过刺激宿主细胞分泌血管内皮生长因子,增加损伤区微血管密度,抑制宿主细胞凋亡等实现的。     

CT引导下脊髓内穿刺骨髓间充质细胞移植治疗脊髓损伤后遗症60例临床疗效分析

目的探讨应用CT引导下脊髓穿刺骨髓间充质细胞移植治疗脊髓损伤后遗症的临床疗效。方法对60例脊髓损伤后遗症患者行CT引导下脊髓穿刺骨髓间充质细胞移植,并进行术前和术后半年ASIA损伤分级评分。结果患者感觉功能、运动功能、日常生活能力明显改善。结论CT引导下脊髓穿刺骨髓间充质细胞移植可以显著改善脊髓损伤后遗症患者的症状和体征,提高患者生活质量。     

脐带间充质干细胞移植治疗遗传性痉挛性截瘫2例

背景：遗传性痉挛性截瘫是一种具有临床及遗传异质性的神经系统遗传病,目前临床治疗无明显效果。 目的：观察脐带间充质干细胞移植治疗遗传性痉挛性截瘫的效果及安全性。 方法：将细胞总数为(2~6)×107个人胎儿脐带间充质干细胞通过静脉输注和腰穿鞘内注射途径移植到自愿接受干细胞移植的2例遗传性痉挛性截瘫患者体内。移植后定期随访观察患者临床症状及各项指标的变化并进行综合分析。 结果与结论：2例患者经脐带间充质干细胞移植治疗后临床症状均明显好转,双下肢肌张力明显降低,不需借助拐杖或他人帮助可独立行走,并且步态平稳,移植后各项生化指标正常,未出现严重的并发症和明显的不良反应。随访1年余2例患者的症状持续缓解无复发。说明脐带间充质干细胞移植治疗遗传性痉挛性截瘫近期疗效明显,可以改善患者的临床症状,延缓病情的进展。     

干细胞移植治疗共济失调七例

目的探讨异体脐带血干细胞移植治疗共济失调的疗效。方法 7例患者接受了干细胞移植,其中女性4例,男性3例。年龄最大73岁,最小4岁,病史最长17年,最短1年。给予患者异体脐带血干细胞6次移植。移植前后按《世界合作共济失调量表》评分,两次评分进行统计学处理。结果 7例患者的《世界合作共济失调量表》评分均下降,最多下降22分,最少下降9.5分,移植前后的评分比较P=0.0001。结论异体脐带血干细胞移植治疗共济失调短期内观察安全、有效。长期疗效尚在随访中     

Stem cell transplantation for spinal cord injury:a meta-analysis of treatment effectiveness and safety

OBJECTIVE: The aim of this study was to evaluate the effectiveness and safety of stem cell transplantation for spinal cord injury(SCI).DATA SOURCES: PubM ed, EMBASE, Cochrane, China National Knowledge Infrastructure, China Science and Technology Journal, Wanfang, and Sino Med databases were systematically searched by computer to select clinical randomized controlled trials using stem cell transplantation to treat SCI, published between each database initiation and July 2016. DATA SELECTION: Randomized controlled trials comparing stem cell transplantation with rehabilitation treatment for patients with SCI. Inclusion criteria:(1) Patients with SCI diagnosed according to the American Spinal Injury Association(ASIA) International standards for neurological classification of SCI;(2) patients with SCI who received only stem cell transplantation therapy or stem cell transplantation combined with rehabilitation therapy;(3) one or more of the following outcomes reported: outcomes concerning neurological function including sensory function and locomotor function, activities of daily living, urination functions, and severity of SCI or adverse effects. Studies comprising patients with complications, without full-text, and preclinical animal models were excluded. Quality of the included studies was evaluated using the Cochrane risk of bias assessment tool and Rev Man V5.3 software, provided by the Cochrane Collaboration, was used to perform statistical analysis. OUTCOME MEASURES: ASIA motor score, ASIA light touch score, ASIA pinprick score, ASIA impairment scale grading improvement rate, activities of daily living score, residual urine volume, and adverse events.RESULTS: Ten studies comprising 377 patients were included in the analysis and the overall risk of bias was relatively low level. Four studies did not detail how random sequences were generated, two studies did not clearly state the blinding outcome assessment, two studies lacked blinding outcome assessment, one study lacked follow-up information, and four studies carried out selective reporting. Compared with rehabilitation therapy, stem cell transplantation significantly increased the lower limb light touch score(odds ratio(OR) = 3.43, 95% confidence interval(CI): 0.01 – 6.86, P = 0.05), lower limb pinprick score(OR = 3.93, 95%CI: 0.74 – 7.12, P = 0.02), ASI grading rate(relative risk(RR) = 2.95, 95%CI: 1.64 – 5.29, P = 0.0003), and notably reduced residual urine volume(OR = –8.10, 95%CI: –15.09 to –1.10, P = 0.02). However, stem cell transplantation did not significantly improve motor score(OR = 1.89, 95%CI: –0.25 to 4.03, P = 0.08) or activities of daily living score(OR = 1.12, 95%CI: –1.17 to 4.04, P = 0.45). Furthermore, stem cell transplantation caused a high rate of mild adverse effects(RR = 14.49, 95%CI: 5.34 – 34.08, P 0.00001); however, these were alleviated in a short time. CONCLUSION: Stem cell transplantation was determined to be an efficient and safe treatment for SCI and simultaneously improved sensory and bladder functions. Although associated minor and temporary adverse effects were observed with transplanted stem cells, spinal cord repair and axon remyelination were apparent. More randomized controlled trials with larger sample sizes and longer follow-up times are needed to further validate the effectiveness of stem cell transplantation in the treatment of SCI.     

脐带间充质干细胞移植治疗帕金森病效果分析

目的 探讨脐带间充质干细胞移植治疗帕金森病的临床效果.方法 选择我院收治的38例帕金森病为研究对象,采用足月妊娠产妇脐带处理后干细胞,于第2周期进行鞘内注射移植治疗.分析治疗后临床症状及体征改善情况.治疗前及治疗后1个月,采用帕金森病统一评分量表（UPDRS）对患者精神、行为、情绪、日常活动、运动功能、并发症进行评价.结果 所有患者的静止性震颤、运动迟缓、肌强直、姿势步态障碍均不同程度缓解,治疗过程中及治疗后患者各项生命体征均较平稳.38例患者移植后UPDRS评分显著低于移植前,差异有统计学意义（P＜0.05）.治疗过程中患者有低热、头痛、腰痛、兴奋症状出现,给予对症处理后均完全缓解.均未见抗移植物宿主病.结论 脐带间充质干细胞移植可显著改善帕金森病患者的临床症状.     

Functional recovery and microenvironmental alterations in a rat model of spinal cord injury following human umbilical cord blood-derived mesenchymal stem cells transplantation

BACKGROUND: Transplantation of human umbilical cord blood-derived mesenchymal stem cells (MSCs) has been shown to benefit spinal cord injury (SCI) repair. However, mechanisms of microenvironmental regulation during differentiation of transplanted MSCs remain poorly understood. OBJECTIVE: To observe changes in nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and interleukin-8 (IL-8) expression following transplantation of human umbilical cord-derived MSCs, and to explore the association between microenvironment and neural functional recovery following MSCs transplantation.DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the Department of Orthopedics, First Affiliated Hospital of Soochow University from April 2005 to March 2007. MATERIALS: Human cord blood samples were provided by the Department of Gynecology and Obstetrics, First Affiliated Hospital of Soochow University. Written informed consent was obtained. METHODS: A total of 62 Wister rats were randomly assigned to control (n = 18), model (n = 22, SCI + PBS), and transplantation (n = 22, SCI + MSCs) groups. The rat SCI model was established using the weight compression method. MSCs were isolated from human umbilical cord blood and cultured in vitro for several passages. 5-bromodeoxyuridine (BrdU)-labeled MSCs (24 hours before injection) were intravascularly transplanted. MAIN OUTCOME MEASURES: The rats were evaluated using the Basso, Beattie and Bresnahan (BBB) locomotor score and inclined plane tests. Transplanted cells were analyzed following immunohistochemistry. Enzyme-linked immunosorbant assay was performed to determine NGF, BDNF, and IL-8 levels prior to and after cell transplantation.RESULTS: A large number of BrdU-positive MSCs were observed in the SCI region of the transplantation group, and MSCs were evenly distributed in injured spinal cord tissue 1 week after transplantation. BBB score and inclined plane test results revealed significant functional improvement in the transplantation group compared to the model group (P< 0.05), which was maintained for 2-3 weeks. Compared to the model group, NGF and BDNF levels were significantly increased in the injured region following MSCs transplantation at 3 weeks (P < 0.05), but IL-8 levels remained unchanged (P > 0.05).CONCLUSION: MSCs transplantation increased NGF and BDNF expression in injured spinal cord tissue. MSCs could promote neurological function recovery in SCI rats by upregulating NGF expression and improving regional microenvironments.     

脐血单核细胞移植治疗慢性完全性脊髓损伤Ⅱ期临床试验的安全性和疗效评估

目的评估人类白细胞抗原（HLA≥4:6）配型的脐血单核细胞（UCBMC）移植治疗慢性完全性脊髓损伤（SCI）的安全性、可行性、有效性以及最佳细胞剂量和联合使用甲基强的松龙（MP）、碳酸锂对细胞移植的作用。 方法选取联勤保障部队第九二〇医院神经外科自2011年2月至2014年1月收治的20例SCI患者,按照随机数字表法分为5组（A、B、C、D、E组）,每组4例受试者。在患者损伤上下缘脊神经背根入处的4个点（上下各2点）注射UCBMC,A、B、C组分别为每点各注射4、8和16 μL（100 000 UCBMC/μL,640万细胞）到SCI部位的上方和下方脊神经背根入处,D组为16 μL细胞注射加30 mg/kg MP静脉注射,E组为16 μL细胞注射加MP和口服碳酸锂（750 mg/d）,一个疗程6周。受试者进行3~6个月的强化步行训练,以美国脊髓损伤协会（ASIA）为主要评分指标,脊髓损伤步行指数（WISCI）和脊髓独立量表（SCIM）为次要评分指标。 结果20例受试者的SCI平面分别位于C3~T11,平均受伤7年。治疗前,16例（80%）患者行走<10 m,18例（90%）患者自理生活需要协助。治疗后41~87周,受试者ASIA运动评分无明显变化,而WISCI和SCIM评分明显提高。15例（75%）患者可在辅助下步行10 m,12例（60%）患者恢复膀胱和肠道控制,5例（25%）患者由完全性SCI变为不完全性SCI;所有患者无神经功能丢失。 结论UCBMC移植和步行训练能提高慢性完全性SCI患者的WISCI和SCIM评分,但对运动评分没有改善,因此推测UCMBC移植能促进轴突的生长,从而激活中枢模式发生器,改善运动、排尿和排便等功能,而且联合使用MP和碳酸锂对细胞移植治疗无明显作用。     

Progress in clinical trials of cell transplantation for the treatment of spinal cord injury:how many questions remain unanswered?

Spinal cord injury can lead to severe motor,sensory and autonomic nervous dysfunctions.However,there is currently no effective treatment for spinal cord injury.Neural stem cells and progenitor cells,bone marrow mesenchymal stem cells,olfactory ensheathing cells,umbilical cord blood stem cells,adipose stem cells,hematopoietic stem cells,oligodendrocyte precursor cells,macrophages and Schwann cells have been studied as potential treatments for spinal cord injury.These treatments were mainly performed in animals.However,subtle changes in sensory function,nerve root movement and pain cannot be fully investigated with animal studies.Although these cell types have shown excellent safety and effectiveness in various animal models,sufficient evidence of efficacy for clinical translation is still lacking.Cell transplantation should be combined with tissue engineering scaffolds,local drug delivery systems,postoperative adjuvant therapy and physical rehabilitation training as part of a comprehensive treatment plan to provide the possibility for patients with SCI to return to normal life.This review summarizes and analyzes the clinical trials of cell transplantation therapy in spinal cord injury,with the aim of providing a rational foundation for the development of clinical treatments for spinal cord injury.     

Stem cell transplantation for treating spinal cord injury A literature comparison between studies of stem cells obtained from various sources

OBJECTIVE:To identify global research trends of stem cell transplantation for treating spinal cord injury using a bibliometric analysis of the Web of Science.DATA RETRIEVAL:We performed a bibliometric analysis of data retrievals for stem cell transplantation for treating spinal cord injury from 2002 to 2011 using the Web of Science.SELECTION CRITERIA:Inclusion criteria:(a) peer-reviewed articles on stem cell transplantation for treating spinal cord injury that were published and indexed in the Web of Science;(b) type of articles:original research articles,reviews,meeting abstracts,proceedings papers,book chapters,editorial material,and news items;and(c) year of publication:2002-2011.Exclusion criteria:(a) articles that required manual searching or telephone access;(b) documents that were not published in the public domain;and(c) a number of corrected papers from the total number of articles.MAIN OUTCOME MEASURES:(1) Annual publication output;(2) distribution according to country;(3) distribution according to institution;(4) distribution according to journals;(5) distribution according to funding agencies;and(6) top cited articles over the last 10 years.RESULTS:Bone marrow mesenchymal stem cells and embryonic stem cells have been widely used for treating spinal cord injury.In total,191 studies of bone marrow mesenchymal stem cell transplantation and 236 studies of embryonic stem cell transplantation for treating spinal cord injury appeared in the Web of Science from 2002 to 2011,and almost half of which were derived from American or Japanese authors and institutes.The number of studies of stem cell transplantation for treating spinal cord injury has gradually increased over the past 10 years.Most papers on stem cell transplantation for treating spinal cord injury appeared in journals with a particular focus on stem cell research,such as Stem Cells and Cell Transplantation.Although umbilical cord blood stem cells and adipose-derived stem cells have been studied for treating spinal cord injury,the number of published papers was much smaller,with only 21 and 17 records,respectively,in the Web of Science.CONCLUSION:Based on our analysis of the literature and research trends,we found that stem cells transplantation obtained from various sources have been studied for treating spinal cord injury;however,it is difficult for researchers to reach a consensus on this theme.     

Human umbilical cord mesenchymal stem cells to treat spinal cord injury in the early chronic phase: study protocol for a prospective,multicenter, randomized,placebo-controlled,single-blinded clinical trial

Human umbilical cord mesenchymal stem cells(hUC-MSCs)support revascularization,inhibition of inflammation,regulation of apoptosis,and promotion of the release of beneficial factors.Thus,they are regarded as a promising candidate for the treatment of intractable spinal cord injury(SCI).Clinical studies on patients with early chronic SCI(from 2 months to 1 year post-injury),which is clinically common,are rare;therefore,we will conduct a prospective,multicenter,randomized,placebo-controlled,single-blinded clinical trial at the Third Affiliated Hospital of Sun Yat-sen University,West China Hospital of Sichuan University,and Shanghai East Hospital,Tongji University School of Medicine,China.The trial plans to recruit 66 early chronic SCI patients.Eligible patients will undergo randomization at a 2:1 ratio to two arms:the observation group and the control group.Subjects in the observation group will receive four intrathecal transplantations of stem cells,with a dosage of 1×106/kg,at one calendar month intervals.Subjects in the control group will receive intrathecal administrations of 10 mL sterile normal saline in place of the stem cell transplantations.Clinical safety will be assessed by the analysis of adverse events and laboratory tests.The American Spinal Injury Association(ASIA)total score will be the primary efficacy endpoint,and the secondary efficacy outcomes will be the following:ASIA impairment scale,International Association of Neural Restoration-Spinal Cord Injury Functional Rating Scale,muscle tension,electromyogram,cortical motor and cortical sensory evoked potentials,residual urine volume,magnetic resonance imaging–diffusion tensor imaging,T cell subtypes in serum,neurotrophic factors and inflammatory factors in both serum and cerebrospinal fluid.All evaluations will be performed at 1,3,6,and 12 months following the final intrathecal administration.During the entire study procedure,all adverse events will be reported as soon as they are noted.This trial is designed to evaluate the clinical safety and efficacy of subarachnoid transplantation of hUC-MSCs to treat early chronic SCI.Moreover,it will establish whether cytotherapy can ameliorate local hostile microenvironments,promote tracking fiber regeneration,and strengthen spinal conduction ability,thus improving overall motor,sensory,and micturition/defecation function in patients with early chronic SCI.This study was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University,China(approval No.[2018]-02)on March 30,2018,and was registered with ClinicalTrials.gov(registration No.NCT03521323)on April 12,2018.The revised trial protocol(protocol version 4.0)was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University,China(approval No.[2019]-10)on February 25,2019,and released on ClinicalTrials.gov on April 29,2019.     

促红细胞生成素联合甲强龙对脊髓损伤病人神经功能的影响

目的 探讨促红细胞生成素（EPO）联合甲强龙对脊髓损伤（SCI）病人神经功能的影响。方法 回顾性分析2018年1~12月收治的60例SCI的临床资料。采用EPO联合甲强龙治疗30例（观察组）,单用甲强龙治疗30例（对照组）。甲强龙首次用量30 mg/kg,在15 min内静脉注射,1 h后以5.4 mg/（kg·h）维持治疗24 h后;EPO治疗,3 000 IU/次,3次/周,持续8周。治疗前及治疗后1个月按照美国脊髓损伤协会（ASIA）评分评估神经功能,采用日常生活活动能力（ADL）评分评估生活能力。治疗前、治疗后2周检测红细胞和血红蛋白水平,准确记录两组病人治疗2周内并发症情况。结果 治疗前,两组ASIA评分、ADL评分、红细胞、血红蛋白水平均无统计学差异（P>0.05）。治疗后,两组ASIA评分、ADL评分、红细胞、血红蛋白水平均明显增高（P<0.05）,而且,观察组明显高于对照组（P<0.05）。观察组并发症发生率明显低于对照组（P<0.05）。结论 EPO联合甲强龙治疗有利于促进SCI病人神经功能的恢复,减少并发症,具有很好的临床疗效。     

Human umbilical cord blood stem cell transplantation for the treatment of chronic spinal cord injury Electrophysiological changes and long-term efficacy

Stem cell transplantation can promote functional restoration following acute spinal cord injury (injury time < 3 months), but the safety and long-term efficacy of this treatment need further exploration. In this study, 25 patients with traumatic spinal cord injury (injury time > 6 months) were treated with human umbilical cord blood stem cells via intravenous and intrathecal injection. The follow-up period was 12 months after transplantation. Results found that autonomic nerve functions were restored and the latent period of somatosensory evoked potentials was reduced. There were no severe adverse reactions in patients following stem cell transplantation. These experimental findings suggest that the transplantation of human umbilical cord blood stem cells is a safe and effective treatment for patients with traumatic spinal cord injury.