脐带间充质干细胞治疗脊髓小脑性共济失调12例**

背景：目前尚未见应用脐带间充质干细胞治疗脊髓小脑性共济失调的报道。 目的：观察脐带间充质干细胞治疗脊髓小脑性共济失调的临床效果。 方法：选择2010-09/12解放军455医院干细胞移植中心收治的12例脊髓小脑共济失调患者,给予脐带间充质干细胞鞘内注射,每次107个细胞,1次/周,4次为1个疗程。 结果与结论：患者治疗后1个月与治疗前比较国际合作共济失调评分量表评分及日常生活量表评分均明显降低(P < 0.05),提示患者的神经功能显著改善,总有效率为16.7%。说明脐带间充质干细胞鞘内注射治疗可以在一定程度上改善脊髓小脑性共济失调患者的临床症状,提高患者生活质量。     

自体骨髓间充质干细胞回输对脑性瘫痪儿童运动功能发育的影响

背景：自体骨髓干细胞对神经系统疾病具有一定的治疗作用,但对脑瘫治疗缺乏系统有对照的临床研究。 目的：分析自体骨髓间充质干细胞移植对脑性瘫痪儿童运动功能发育的影响。 方法：将34例脑性瘫痪者按其家长是否同意使用自体骨髓干细胞移植治疗分为治疗组和对照组,治疗组采取自体骨髓间充质干细胞移植结合康复训练,对照组只采用康复训练,分别在治疗前和治疗后3个月做粗大运动功能测试量表(GMFM)评估并进行对比。 结果与结论：与治疗前比较,2组治疗后3个月GMFM评分均增高,而GMFM评分增加量均降低,差异均有显著性意义 (P < 0.05)。治疗组GMFM评分增加量高于对照组(P < 0.05)。 提示自体骨髓间充质干细胞移植治疗脑性瘫痪是有效的,对促进脑性瘫痪患儿运动功能发育有积极作用。     

干细胞移植治疗糖尿病足

背景：以自体骨髓、脐血单个核细胞移植治疗糖尿病足,对缺血性病变及周围神经损伤所致临床症状有改善作用,对糖尿病足也有较好的疗效。脐带间充质干细胞与骨髓干细胞和脐血干细胞相比有其自身的优势。 目的：观察脐带间充质干细胞移植治疗糖尿病足病缺血及神经损伤的疗效。 方法：选取2010至2012年住院行脐带间充质干细胞移植治疗的糖尿病足病患者32例,将脐带间充质干细胞稀释后行双下肢肌肉内注射,每个注射点间隔约3 cm,每个肢体移植(5.02±1.37) ×108个。于3个月和6个月后评价其下肢缺血和下肢周围神经病变情况。并检索CNKI数据库,对国内干细胞移植治疗糖尿病足的研究状况进行分析。 结果与结论：移植后踝肱指数升降不一,移植后6个月疼痛评分及冷感评分明显改善,间歇性跛行及皮肤温度、经皮氧分压治疗后3,6个月与移植前比较差异均有显著性意义;对神经病变损伤自觉症状评分、临床检查评分、振动感觉阀值移植后6个月与移植前比较差异有显著性意义。腓浅神经、胫神经感觉神经传导速度,腓总神经、胫神经运动神经传导速度,在移植后3个月与移植前比较,差异无显著性意义(P > 0.05),移植6个月与移植前相比较有升高,差异有显著性意义(P < 0.05)。可见脐带间充质干细胞可以改善糖尿病缺血性病变及周围神经病变的临床症状及客观指标。文献分析结果发现,已有的研究中治疗结果都比较理想,多数研究中的移植方法为进行肌肉注射。     

脐血单个核细胞和脐带间充质干细胞治疗儿童孤独症的安全性与有效性

背景：目前国内外尚没有治疗儿童孤独症的金标准,康复治疗效果不佳。 目的：评价脐血单个核细胞和脐带间充质干细胞治疗儿童孤独症的临床安全性和有效性。 方法：37例儿童孤独症患者非随机分为脐血组、混合组和对照组。脐血组应用脐血单个核细胞加康复训练治疗;混合组联合应用脐血单个核细胞和脐带间充质干细胞加康复训练治疗;对照组单纯行康复训练治疗。脐血组和混合组患者在干细胞治疗前和首次治疗后1,2,6个月分别行相关指标实验室检查,并观察有无不良反应发生。3组患者在治疗前和首次治疗后1,2,6个月分别行儿童孤独症评定量表(CARS)和异常行为量表(ABC)评估。 结果与结论：脐血组和混合组患者在干细胞治疗前和首次治疗后1,2,6个月相关指标实验室检查未发现有意义异常变化,干细胞治疗后无严重不良反应发生;根据CARS和ABC评分,3组治疗均有效,其疗效比较：混合组优于脐血组,脐血组优于对照组。     

脐血间充质干细胞移植脊髓损伤恢复期患者的免疫功能变化*

背景：间充质干细胞移植因其具有一定的免疫原性,对脊髓损伤患者免疫功能的影响尚无深入系统的报道。 目的：观察脐血源间充质干细胞移植对脊髓损伤患者免疫功能的影响。 方法：61例脊髓损伤患者采用静脉滴注结合腰椎脊髓蛛网膜下腔注射脐血间充质干细胞悬液治疗。应用流式细胞术及免疫比浊法分别测定患者移植前后T淋巴细胞亚群、免疫球蛋白及补体的含量。 结果与结论：与治疗前相比,患者CD3+、IgA及IgG有下降趋势,差异有显著性意义;CD4+、CD8+、CD4+/CD8+、IgM、C3及C4均有升高或下降趋势,但差异无显著性意义。提示脐血源间充质干细胞移植对细胞及体液免疫不会激活急性免疫应答,移植是安全的,存在负向免疫调节作用的可能,但尚需进一步完善相关指标,扩大样本,明确相关机制。 关键词：脐血源间充质干细胞;细胞移植;脊髓损伤;免疫功能;T淋巴细胞亚群;免疫球蛋白;补体 doi:10.3969/j.issn.1673-8225.2012.01.037     

人脐血单个核细胞移植治疗急性一氧化碳中毒后迟发脑病1年随访

背景：研究报道在特定的体内外环境下,脐血间充质干细胞能够诱导分化成为包括神经干细胞在内的多种组织细胞。 目的：评价人脐血单个核细胞经腰穿途径移植后治疗急性一氧化碳中毒后迟发性脑病的疗效及安全性。 方法：一氧化碳中毒后迟发性脑病患者60例随机分为2组。对照组给予高压氧及药物治疗;治疗组采用鞘内注射法将经密度梯度离心法分离出的人脐血单个核细胞移植到一氧化碳中毒性脑病患者的蛛网膜下腔,余治疗方法同对照组。分别于人脐血单个核细胞移植前、移植后3,9,12个月对患者进行简易精神状态检查法、改良Asworth肌肉痉挛程度分级及日常生活量表评分检查;比较两组患者MRI变化;同时对随诊患者行胸片、心电图及血生化检查,客观评价人脐血单个核细胞移植的安全性。 结果与结论：人脐血单个核细胞移植3,9,12个月,治疗组Asworth肌肉痉挛程度分级评分均显著低于对照组(P=0.032);移植后9,12个月简易智力状况检查法及日常生活量表评分均显著高于对照组(P < 0.05);两组患者神经功能在各时间点的变化趋势相似。人脐血单个核细胞移植后12个月MRI检查结果显示,治疗组患者MRI改善程度较对照组明显。提示鞘内注射移植人脐血单个核细胞治疗一氧化碳中毒后迟发脑病疗效优于高压氧治疗。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

自体外周血干细胞移植治疗肌萎缩侧索硬化患者9例：短期效果分析

背景：目前临床报道已有关于自体骨髓有核细胞、嗅细胞、脐血源干细胞移植治疗肌萎缩侧索硬化的报道。 目的：观察自体外周血干细胞移植治疗9例肌萎缩侧索硬化患者的临床疗效。 方法：采用自身前后对照研究方法,对9例肌萎缩侧索硬化患者自体外周血干细胞移植前和移植后第1,3,6个月神经功能改变(FIM、Norris、Bathel评分)及肌电图改变进行评估。 结果与结论：自体外周血干细胞移植后自我症状改善,神经功能评分显著高于移植前,短期内效果明显,肌电图呈现改善趋势。结果初步表明自体外周血干细胞移植治疗可在一定程度上改善肌萎缩侧索硬化患者神经功能障碍。关键词：肌萎缩侧索硬化;自体外周血;干细胞移植;神经功能评分;肌电图 缩略语注释：ALS：amyotrophic lateral sclerosis,肌萎缩侧索硬化 doi:10.3969/j.issn.1673-8225.2012.14.036     

脐血间充质干细胞移植治疗多发性肌炎/皮肌炎：Th细胞因子的变化

背景：近年来,应用干细胞治疗免疫性疾病已成为研究热点,国内外有关脐血间充质干细胞移植治疗多发性肌炎/皮肌炎的报道较少。目的：观察脐血间充质干细胞移植治疗多发性肌炎/皮肌炎患者血清干扰素γ、白细胞介素4、白细胞介素17水平变化,探讨Th细胞因子在多发性肌炎/皮肌炎发生发展中的免疫机制。方法：81例多发性肌炎/皮肌炎患者,其中44例为常规治疗组,给予糖皮质激素联合免疫抑制剂治疗,37例为脐血间充质干细胞移植组,静脉输注脐血间充质干细胞(3.5-5.2)×10⁷,用药方案与常规治疗组相同。随访治疗后1,3,6 个月肌酸激酶、肌力变化及治疗后3,6个月肺部影像学改变,并在治疗前及治疗后3,6个月检测移植组Th细胞因子水平。结果与结论：①两组治疗后1,3,6个月与治疗前比较肌酸激酶值明显下降、肌力评分明显增高(均P < 0.001);移植组治疗后各时间点肌酸激酶值较常规治疗组低、肌力评分较常规治疗组高(均P < 0.001)。②脐血间充质干细胞移植治疗能明显改善肺部影像学异常,且安全性好。③移植治疗后6个月干扰素γ水平显著升高,而白细胞介素4水平显著下降(均P < 0.01);移植治疗后 3,6 个月白细胞介素17水平显著下降(均P < 0.01)。④移植治疗后6个月白细胞介素4、白细胞介素17水平与肌酸激酶水平成正相关(r=0.467和0.488,均P < 0.05);干扰素γ水平与肌酸激酶水平无明显相关(r=0.213,P > 0.05)。结果表明给予糖皮质激素及免疫抑制剂治疗同时,联合脐血间充质干细胞移植治疗多发性肌炎/皮肌炎安全、有效,可调节多发性肌炎/皮肌炎患者免疫网络效应、改善免疫耐受。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

间充质干细胞治疗脊髓小脑性共济失调

背景：脊髓小脑性共济失调是临床上较常见的以进行性加重的四肢共济运动障碍为主要临床表现的中枢神经系统变性疾病,常规药物治疗效果欠佳。 目的：观察自体骨髓间充质干细胞以及异体脐带间充质干细胞输注治疗脊髓小脑性共济失调的临床效果。 方法：对接受间充质干细胞治疗的27例确诊脊髓小脑性共济失调患者进行综合统计分析,其中6例行自体骨髓间充质干细胞腰穿治疗,21例行异体脐带间充质干细胞腰穿结合静脉输注治疗,两组患者均采用世界神经病联合会国际合作共济失调量表(International Cooperative Ataxia Rating Scale,ICARS)对患者治疗前后神经功能进行评定。 结果与结论：所有27例脊髓小脑共济失调患者行间充质干细胞治疗过程中以及治疗前后均未及明显不良反应。其中6例患者采用自体骨髓间充质干细胞治疗后效果均不明显,另外21例患者行异体脐带间充质干细胞输注治疗,治疗后3个月与治疗前比较,患者自觉症状均有一定程度改善,ICARS评分明显降低(P < 0.05)。说明脐带间充质干细胞治疗是安全的,可以一定程度地改善脊髓小脑性共济失调患者的临床症状,提高患者生活质量。     

单倍体相合造血干细胞移植治疗儿童重型再生障碍性贫血

背景：目前治疗儿童再生障碍性贫血的主要方法为强化免疫抑制治疗或干细胞移植,后者由于供者来源少而受到限制,HLA单倍体相合的异基因造血干细胞在白血病治疗中常见应用,在再生障碍性贫血治疗中较少应用。目的：探讨单倍体相合的造血干细胞移植联合胎盘来源的间充质干细胞移植治疗重型儿童再生障碍性贫血的疗效。方法：患儿,女,7岁,确诊重型再生障碍性贫血1年半,2012-07-09接受HLA单倍体相合的异基因骨髓及外周血单个核细胞联合胎盘来源间充质干细胞移植,供者为母亲。预处理采用氟达拉滨联合环磷酰胺和抗胸腺细胞球蛋白方案。结果与结论：移植后+9 d中性粒细胞>0.5×10⁹ L^-1,+12 d完成造血重建,+100 d查STR提示植入完成。移植后+8个月停用免疫抑制药物,未发生急、慢性移植物抗宿主病。患儿随访18个月,无病生存。结果表明,HLA单倍体相合的造血干细胞联合胎盘来源间充质细胞移植治疗儿童重型再生障碍性贫血是一种安全有效、值得探索的方法。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

慢性脊髓性肌萎缩的电生理改变及肌活检

目的:探讨慢性脊髓性肌萎缩(SMA)患者的肌电图及肌活检的诊断价值。方法:对38例SMA病人进行肌电图和肌活检检查。结果:肌电图除3例正常外,其余表现为神经原性损害;光镜提示神经原性萎缩。结论:提示肌电图在SMA的确诊有重要价值。     

肌酸磷酸激酶增高的脊髓性肌萎缩症患者临床与肌电图分析

目的：观察血清肌酸磷酸激酶（CK）增高的脊髓性肌萎缩症（SMA）患者临床与肌电图的关系。方法：收集10例CK增高的SMA病例，进行临床及肌电图分析，其中6例作了肌肉活检。结果：CK增高可见于脊髓性肌萎缩各型，升高的程度各有不同。肌电图检查除2例为混合性损害外，余8例均为神经源性损害。肌肉活检除1例为肌性改变外，余均为神经源性肌萎缩。结论：CK增高不能作为SMA与进行性肌营养不良的鉴别诊断指标。在诊断SMA时，当肌活检为肌性损害，反复多次的肌电图的结果更可靠；当肌电图结果不明确时，肌活检结果为确定诊断的最可靠依据。     

The use of fractional parameter in analyzing motor unit discharge pattern in stroke patients: a correlation with the functional independence measurement

BACKGROUND: We have previously demonstrated that the fractional parameter has significant correlation with the muscle strength of patients with stroke. In this study, we have investigated whether fractional parameter can be used to objectively document stroke patients' functional level (using FIM scores). METHODS: Sixty motor units were recorded in abductor pollicis brevis, first dorsal interosseous, and abductor digiti minimi muscles in 18 stroke patients. Patients' FIM scores, obtained fractional parameters, and serial correlation coefficients were analyzed and statistical determination was made. RESULTS: Statistical significance was found between fractional parameters and motor items of FIMs (except selfcare category); no statistical significant correlation was found between SSC and FIM scores. CONCLUSION: Fractional parameter could be a useful tool for measuring motor function at a single motor unit level.     

Further investigations of the efferent linkage of the supplementary motor area (SMA) with the spinal cord in the monkey

Summary Intracortical microstimulation of the supplementary motor area (SMA) was studied in awake monkeys. With short trains of micropulses, contralateral muscle twitches mainly in shoulder and proximal arm muscles were elicited. There was an indication of a rostro-caudal representation of distal to proximal forelimb, trunk, and proximal to distal hindlimb muscles. However, an intermingling of efferent zones was much more prominent as compared to the precentral motor cortex (MI). All efferent zones to the spinal cord were clustered in the caudal half of the SMA, and we failed to detect face and ocular movements (except at one stimulation site) when microstimulating the rostral portions of the SMA. Single micropulses were also injected in efferent zones of the microexcitable cortex in order to investigate post-pulse facilitation of sustained EMG activity. For motor cortex (MI) stimulation, post-pulse facilitation was prominent and observed in 14 of 17 tested stimulation sites. The incidence of facilitation in comparable muscles obtained with SMA stimulation was only 20 out 54 tests. The onset latencies of EMG modulation obtained from the two areas were in the same range but the amount of modulation in the SMA was less conspicuous than in MI. These results indicate that the SMA has oligo- or possibly even monosynaptic connections with motoneurones, but that these connections are less dense than those from MI.     

脐血间充质干细胞移植治疗低血糖昏迷1例

背景：成体干细胞可以跨系跨胚层分化为所有的组织细胞类型,在特定的条件下,可分化为骨、软骨、脂肪、肌肉和神经细胞等,替代、修复已受损的组织、细胞,达到功能修复的目的。 目的：观察脐血间充质干细胞治疗低血糖昏迷并发缺氧缺血性脑病的疗效。 方法：对收治的1 例低血糖昏迷并发缺氧缺血性脑病及肺部感染的患者,给予抗自由基、营养神经、促醒、抗感染、康复理疗等综合治疗的同时,从静脉滴注进行脐血间充质干细胞治疗。观察住院期间意识恢复情况、脑电图、日常生活能力评分及随访结果。 结果与结论：治疗近1个月后患者运动、认知功能明显恢复,复查脑电图可及a波,日常生活活动能力评分50分,70 d后随访,患者未出现不良反应,表明干细胞治疗近期疗效安全。提示脐血间充质干细胞治疗低血糖昏迷并发缺氧缺血性脑病安全有效。     

Relationship between motor activity-related cortical potential and voluntary muscle activation

The purpose of this study was to investigate the relationship between EEG-derived motor activity-related cortical potential (MRCP) and voluntary muscle activation. Eight healthy volunteers participated in two experimental sessions. In one session, subjects performed isometric elbow-flexion contractions at four intensity levels [10%, 35%, 60%, and 85% maximal voluntary contraction (MVC)]. In another session, a given elbow-flexion force (35% MVC) was generated at three different rates (slow, intermediate, and fast). Thirty to 40 contractions were performed at each force level or rate. EEG signals were recorded from the scalp overlying the supplementary motor area (SMA) and contralateral sensorimotor cortex, and EMG signals were recorded from the skin surface overlying the belly of the biceps brachii and brachioradialis muscles during all contractions. In each trial, the force was used as the triggering signal for MRCP averaging. MRCP amplitude was measured from the beginning to the peak of the negative slope. The magnitude of MRCP from both EEG recording locations (sensorimotor cortex and SMA) was highly correlated with elbow-flexion force, rate of rising of force, and muscle EMG signals. These results suggest that MRCP represents cortical motor commands that scale the level of muscle activation.     

Increased IGF-1 in muscle modulates the phenotype of severe SMA mice

Spinal muscular atrophy (SMA) is an inherited motor neuron disease caused by the mutation of the survival motor neuron 1 (SMN1) gene and deficiency of the SMN protein. Severe SMA mice have abnormal motor function and small, immature myofibers early in development suggesting that SMN protein deficiency results in retarded muscle growth. Insulin-like growth factor 1 (IGF-1) stimulates myoblast proliferation, induces myogenic differentiation and generates myocyte hypertrophy in vitro and in vivo. We hypothesized that increased expression of IGF-1 specifically in skeletal muscle would attenuate disease features of SMAΔ7 mice. SMAΔ7 mice overexpressing a local isoform of IGF-1 (mIGF-1) in muscle showed enlarged myofibers and a 40% increase in median survival compared with mIGF-1-negative SMA littermates (median survival = 14 versus 10 days, respectively, log-rank P = 0.025). Surprisingly, this was not associated with a significant improvement in motor behavior. Treatment of both mIGF-1(NEG) and mIGF-1(POS) SMA mice with the histone deacetylase inhibitor, trichostatin A (TSA), resulted in a further extension of survival and improved motor behavior, but the combination of mIGF-1 and TSA treatment was not synergistic. These results show that increased mIGF-1 expression restricted to muscle can modulate the phenotype of SMA mice indicating that therapeutics targeted to muscle alone should not be discounted as potential disease-modifying therapies in SMA. IGF-1 may warrant further investigation in mild SMA animal models and perhaps SMA patients.     

A clinical and genetic study of spinal muscular atrophy

AIMS: This study evaluates clinical, electromyography (EMG) and genetic analysis of consecutive patients with spinal muscular atrophy (SMA) in a tertiary care adult neurology practice in India. METHODS: Consecutive patients with SMA attending the neurology out patient department during 2001-2003 were included. They were subjected to a detailed clinical examination, nerve conduction and EMG and muscle biopsy. Clinically patients were classified into generalised and segmental SMA. SMN gene deletion study was carried out in all the patients. RESULTS: There were 15 patients with type III and type IV SMA and 15 with segmental SMA (Hirayama disease). The age ranged between 5 and 23 years in type III SMA, 33-50 years in type IV SMA and 16-30 years in Hirayama disease (HD). The latter was found exclusively in males. Family history was observed in 1 patient each in all the groups. In SMA III mother and brother were affected, in SMA IV two siblings and in HD one brother had similar disease. One type III SMA family was associated with deafness and one type IV family had strong association with maturity onset diabetes in young. The EMG was characterised by lack of fibrillations in all type III and IV SMA patients except 1 whereas in HD, 11 out of 15 had fibrillations suggesting ongoing denervation. The EMG was suggestive of reinnervation in generalised SMA in both upper and lower limb muscles where as these abnormalities were restricted to C7-T1 mytomes in HD. Muscle biopsy in 10 patients with generalised SMA revealed group atrophy in all, and loss of fascicular architecture in 3, clumping of nuclei in 7 and hypertrophic fibers in 4. SMN1 gene deletion was present in 3 patients with type III but none in type IV and HD. CONCLUSION: SMN gene deletion was positive in 33% type III SMA whereas it was negative in type IV and HD. Presence of HD only in males may be consistent with X-linked disorder.     

干细胞及组织移植治疗甲状腺功能减退症

背景：干细胞及甲状腺组织移植治疗甲状腺功能减退症已经取得了一定的成果。 目的：回顾分析干细胞与组织移植治疗甲状腺功能减退症的基础和临床研究进展。 方法：由作者检索1980/2010 PubMed 数据库及万方数据库有关干细胞与甲状腺移植治疗甲状腺功能减退症的基础和临床研究。 结果与结论：自体甲状腺组织移植治疗不可逆性甲状腺功能减退症的作用是肯定的,但存在不足之处,比如需要移植多少甲状腺组织才能使甲状腺功能保持在正常状态,移植后的长期效果还需要更多样本、更长期的跟踪随访来评价。胚胎干细胞在体外环境下可诱导分化为甲状腺细胞,但受伦理学和细胞移植排斥反应等原因困扰。脐血间充质干细胞具有来源丰富、易于采集、保存和运输、无异体排斥、避免伦理争议等诸多优点,在不同诱导条件下能够向不同谱系分化,已被广泛用于治疗各种疾病,但能否通过多种途径诱导其分化为甲状腺细胞,并通过移植方法来治疗甲状腺功能减退症仍需深入研究。