脐血干细胞移植与神经生长因子联合治疗小儿脑性瘫痪的安全性分析

背景：脐血干细胞移植联合神经生长因子治疗小儿脑性瘫痪是临床研究热点。 目的：分析脐血干细胞移植联合神经生长因子治疗小儿脑性瘫痪疗效及安全性。 方法：选取天津红桥医院儿科2011年11月至2013年2月收治的脑性瘫痪患儿80例,按治疗方法分别分为试验组(n=40)和对照组(n=40),分别接受脐血干细胞移植与神经生长因子联合治疗和单独神经生长因子治疗。 结果与结论：与治疗前相比,2组患儿治疗后脑性瘫痪综合功能评定表及粗大运动功能测量量表分值均有所提高(P < 0.05),且白细胞计数、中性粒细胞分数、总胆红素、丙氨酸氨基转移酶、天冬氨酸氨基转移酶明显升高(P < 0.05),且试验组患儿的治疗效果优于对照组(P < 0.05)。所有患儿未见严重不良反应。说明脐血干细胞移植联合神经生长因子治疗小儿重症脑性瘫痪疗效显著,安全性高。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：     

神经干细胞治疗小儿脑性瘫痪的研究进展

背景：神经干细胞移植给小儿脑性瘫痪的治疗带来了可能。 目的：对国内外应用神经干细胞移植治疗的现状及新进展作一综述。 方法：应用计算机检索CNKI和Pubmed数据库中1999-01/2011-04关于神经干细胞移植治疗脑瘫的文章,在标题和摘要中以“脑瘫,神经干细胞,移植”或“cerebral palsy, neural stem cell, transplantation ”为检索词进行检索。选择文章内容与神经干细胞有关者,同一领域文献则选择近期发表或发表在权威杂志文章。初检得到119篇文献,根据纳入标准选择关于神经干细胞移植治疗脑瘫的28篇文献进行综述。 结果与结论：神经干细胞特别是神经营养素3联合神经干细胞移植对小儿脑瘫的功能康复起着促进作用,给小儿脑瘫的今后的治疗指明了方向。      

人脐血间充质干细胞移植联合神经节苷脂注射治疗脑性瘫痪

BACKGROUND:In recent years, some studies have demonstrated that ganglioside can promote survival and differentiation of umbilical blood cord mesenchymal stem cells in vitro. OBJECTIVE:To observe the effect of injection of human umbilical blood cord mesenchymal stem cells and ganglioside into rat lateral ventricles on neurological functional recovery from cerebral palsy. METHODS:Totally 60 cerebral palsy neonatal rats were delivered from pregnant rats which were modes were given intraperitoneal injection of lipopolysaccharide for 2 successive days on day 17 of gestation. Then those neonatal rats were randomly divided into five groups, including model group (n=10), sham transplantation group (n=10), stem cell transplantation group (n=18), ganglioside group (n=10) and combination group (n=12). Under stereotaxic instrument, umbilical blood cord mesenchymal stem cells or ganglioside were injected into left lateral ventricles of the rat brain, respectively, and the sham transplantation group was given the same volume of phosphate buffered saline. Two rats from the stem cell transplantation group were put to death for immunofluorescence staining at 7, 14, 21 and 28 days after transplantation, respectively, and two rats in the combination group were killed for immunofluorescence staining at 14 days. Besides, all rats were underwent neurologic evaluation at 28 days after transplantation. RESULTS AND CONCLUSION:The umbilical blood cord mesenchymal stem cells could survive, migrate and differentiate, which mainly distributed in the lateral ventricle, hippocampus and cortex. At 14 days after transplantation, positive expressions of BrdU and glial fibrillary acidic protein in the combination group were significantly higher than those in the stem cell transplantation group (P < 0.05). In addition, compared with the model group, the holding time significantly prolonged and foot error times significantly decreased in the latter three groups (P < 0.05), as well as in the combination group compared with the stem cell transplantation and ganglioside groups (P < 0.05). These results indicate that umbilical blood cord mesenchymal stem cells and ganglioside can both improve neurological function of rats with cerebral palsy. Given that ganglioside can promote survival and differentiation of umbilical blood cord mesenchymal stem cells in vivo, the combined transplantation is preferred.     

自体骨髓间充质干细胞移植脑性瘫痪儿童运动功能的评价

背景：干细胞具有修复和替代受损脑组织的潜力,被认为是一种新的治疗小儿脑性瘫痪的方法。 目的：用粗大运动功能测试量表88项及精细运动功能评估量表45项评价自体骨髓间充质干细胞移植对脑性瘫痪患儿运动功能的改善情况。 方法：对20例脑性瘫痪患儿进行自体骨髓间充质干细胞移植治疗,用粗大运动功能测试量表88项及精细运动功能评估量表45项对治疗前及治疗后1,3,6 个月时患儿的粗大及精细运动功能进行评估。 结果与结论：随访过程中有3例患儿失访。顺利完成研究的17例患儿治疗后 1,3,6个月的粗大运动功能测试量表88项总分及A(卧位与翻身)、B(坐位)、C(爬与跪)功能区得分,精细运动功能评估量表45项总分及B(上肢关节活动能力)、C(抓握能力)功能区得分均较移植前显著提高(P < 0.05),以治疗后1个月的提升速度最显著,且未见明显不良反应。提示自体骨髓间充质干细胞移植可改善脑性瘫痪患儿的粗大运动和精细运动功能,对治疗小儿脑性瘫痪是安全、有效、可行的。     

神经康复配合鼠神经生长因子穴位注射治疗小儿脑性瘫痪临床疗效分析

目的 探究神经康复配合鼠神经生长因子穴位注射治疗小儿脑性瘫痪效果。方法 选取2017年3月~2018年2月在我院进行治疗的56例脑性瘫痪患儿,将其随机分为研究组和常规组,每组28例。对常规组患儿行常规康复治疗,对研究组患儿行神经康复配合鼠神经生长因子穴位注射治疗,比较两组患儿运动功能及智能水平。结果 两组患者治疗后,其GMFM88评分均有所改善,且研究组治疗后GMFM88评分为（1.21±0.38）分,优于常规组的（1.21±0.38）分及治疗前（P＜0.05）,且两组患者经治疗后,其各项Gesell评分均有所改善,且研究组患者治疗后总发育商、大运动及语言评分分别为（57.86±6.38）分、（62.39±5.41）分及（62.39±6.17）分,均优于常规组（P＜0.05）。结论 对脑性瘫痪患儿采用神经康复配合鼠神经生长因子穴位注射进行治疗,能够显著改善其运动功能及智力水平,对促进患儿生长发育具有重要意义。     

脐血单个核细胞移植治疗痉挛型小儿脑性瘫痪的安全性

背景：大量研究证实脐血间充质干细胞体外培养可被诱导分化为表达神经元和神经胶质细胞表面标志物的细胞,对神经系统疾病起到替代修复的作用。 目的：观察人脐血单个核细胞移植治疗痉挛型小儿脑性瘫痪的疗效和安全性。 方法：收集正常足月剖腹产胎儿的脐血,经肝素抗凝,用淋巴细胞分离液分离脐血单个核细胞,采用差速贴壁法进行纯化,并经腰椎穿刺注入30例痉挛型脑性瘫痪患者体内。 结果与结论：移植后患者肢体的肌肉痉挛程度和关节活动度明显改善,与移植前相比差异有显著性意义(P < 0.05),移植后和随访过程中无不良反应和并发症。     

干细胞在脑性瘫痪治疗中的应用

背景：干细胞在适当条件下可以分化为神经元细胞、星形胶质细胞与少突胶质细胞,可能从根本上改善脑性瘫痪患儿神经元缺失及神经胶质细胞变性,进而改善患儿脑功能障碍,从理论上达到根治目的。 目的：回顾性分析不同来源干细胞经不同途径治疗脑性瘫痪患儿的疗效。 方法：由第一作者检索1992/2011 PubMed数据及万方数据库有关脑性瘫痪的治疗及不同来源干细胞在治疗脑性瘫痪等方面的文献。 结果与结论：神经干细胞在动物神经功能损伤中的修复作用已有很多国内外报道,但目前其在人体的临床应用仍处于临床试验阶段。虽然胚胎、骨髓血、胎儿脐带血、脐带来源的干细胞已在部分医院应用到脑性瘫痪患儿中,并取得了初步的疗效,其具体评定标准及长期疗效仍有待进一步随访、观察。     

针刺联合胎盘间充质干细胞治疗脑性瘫痪大鼠模型

BACKGROUND:Both of acupuncture and mesenchymal stem cell transplantation have therapeutic effects on cerebral palsy. OBJECTIVE:To explore the therapentic effect of acupuncture combined with placenta derived mesenchymal stem cells on rat cerebral palsy. METHODS:Thirty-five Wistar rats were equivalently randomized into five groups, including control group, model group, acupuncture group, transplantation group and combination group. Rat models of cerebral palsy were prepared in all groups except the control group. At 7 days after modeling, in the transplantation group, 10 μL placenta derived mesenchymal stem cells were transplanted into the right cerebral cortex and striatum of rats; rats in theacupuncture group were given acupuncture at Shuigou (DU26), Dazhui (DU14), Baihui (DU20), Guanyuan (RN4) and Qihai (RN6) points; rats in the combination group given acupuncture and transplantation treatment as described above; the model and control groups received no treatment. Then, after 7-day intervention, the body mass, neurological function and pathological changes of rat brain tissues were measured and observed, respectively.  . RESULTS AND CONCLUSION:The order of the growth rate of body mass was as follows: control group > combination group > acupuncture and transplantation groups > model group, and all groups had significant differences except the two groups of acupuncture and transplantation (P < 0.05); findings from holding tract, foot error and water finding in maze tests showed the neurological function was best in the control group, followed by the combination group, as well as acupuncture and transplantation groups, and the worst in the model group. All groups had significant differences except acupuncture and transplantation groups (P < 0.05). Besides, in the model group, cells in the brain and hippocampus decreased, arranging disorderly with fuzzy structure, and inflammatory cells appeared; pathological changes in the other groups were in between control group and model group, Additionally, brain tissues in the combination group exlibited better pathological changes than those in the acupuncture and transplantation groups, which were similar with the normal brain tissues. To conclude, acupuncture, placenta derived mesenchymal stem cells transplantation, or their combination can improve neurological function in rats with cerebral palsy, especially the combination treatment.     

小儿脑性瘫痪与先天畸形相关性研究

目的探讨小儿脑性瘫痪与先天畸形发生之间的关系。方法按照1:4比例随机抽取2000年1月～2004年12月200例脑性瘫痪住院患者和800例非脑性瘫痪住院患者进行先天畸形对照研究,分析先天畸形发生率。结果脑性瘫痪儿童先天畸形22例,发生率为110.00‰,非脑性瘫痪儿童先天畸形15例,发生率为18.75‰。结论脑性瘫痪儿童先天畸形发生率明显高于非脑性瘫痪儿童,先天畸形儿童应注意早期排除存在脑性瘫痪的可能。     

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。     

脐带间充质干细胞移植并康复治疗脑出血后遗症1年随访

背景：人脐带间充质干细胞具有定向分化为神经细胞的潜能,并且已在体内外实验中得到证实。临床有关脐带间充质干细胞移植治疗脑出血的报道较少。 目的：观察人脐带间充质干细胞移植联合综合康复治疗对脑出血后遗症的治疗效果。 方法：脑出血患者45例按照入院单双日分为2组,治疗组22例,对照组23例。常规治疗10~18 d后,存在不同程度的后遗症,治疗组通过介入途径行人脐带间充质干细胞移植及康复治疗,对照组仅给予康复治疗。 结果与结论：所有病例均获12个月随访。两组治疗后1,3,6,12个月Fugl-Meyer评分及改良Barthel指数均显著高于治疗前(P < 0.05),治疗后治疗组Fugl-Meyer评分及改良Barthel指数均显著高于对照组(P < 0.05),肢体运动功能及日常生活活动能力均明显改善。治疗组治疗后3个月功能改善更为明显,配合综合康复治疗有协同并弥补其不足的优点,通过颅脑MRI检查及各项相关生化检查表明其有效性及安全性。提示来源于脐带中的间充质干细胞体外培养后移植治疗脑出血后遗症,无特殊不良反应,配合综合康复治疗可达到功能恢复的较好效果。      

针刺联合神经干细胞移植对脑性瘫痪幼鼠模型的作用机制

背景：针灸治疗脑性瘫痪效果显著,神经干细胞治疗也可以改善脑性瘫痪症状,对于针灸和神经干细胞联合治疗脑性瘫痪的研究较少。 目的：观察针刺和神经干细胞联合治疗对脑性瘫痪鼠的影响及其作用机制。 方法：建立幼鼠脑性瘫痪模型,分别给与单纯针刺、单纯神经干细胞移植、针刺和神经干细胞联合治疗,同时设正常对照组和模型组作对比。 结果与结论：与模型组、单纯针刺组、单纯神经干细胞移植组相比,针刺和神经干细胞联合治疗组的脑性瘫痪幼鼠行为学评分明显改善(P < 0.05),神经细胞数量和Bcl-2蛋白表达增高(P < 0.05),凋亡神经细胞数量和Bax蛋白表达降低(P < 0.05)。模型组、单纯针刺组、单纯神经干细胞移植组上述各指标变化差异不显著。结果说明,针刺+神经干细胞联合治疗可以明显改善脑性瘫痪幼鼠的运动学习和记忆能力,减轻神经细胞凋亡,其机制可能与其抑制Bax蛋白表达,上调Bcl-2蛋白表达有关。 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     

Umbilical cord blood immunology: relevance to stem cell transplantation

Because of its easier accessibility and less severe graft-versus-host disease, umbilical cord blood (UCB) has been increasingly used as an alternative to bone marrow for hematopoietic stem cell transplantation. Naiveté of UCB lymphocytes, however, results in delayed immune reconstitution and infection-related mortality in transplant recipients. This review updates the phenotypic and functional deficiencies of various immune cell populations in UCB compared with their adult counterparts and discusses clinical implications and possible therapeutic strategies to improve the outcome of stem cell transplantation.     

脐血干细胞移植联合电针治疗促进脊髓损伤神经功能恢复

目的:观察脐血干细胞移植联合督脉电针治疗对脊髓全横断损伤大鼠神经功能的恢复作用。方法:建立SD大鼠胸段脊髓完全横断模型,随机分为损伤模型组、脐血干细胞移植组(脐血组)、督脉电针治疗组(电针组)和脐血干细胞移植联合督脉电针治疗组(联合组);梯度离心法分离人脐血单个核细胞,尾静脉注射移植;取大椎、命门二穴,电针治疗。应用Basso-Beattie-Bresnahan(BBB)评分评价各组大鼠后肢功能的恢复情况;各组分别于7、14和28 d 3个时间点检测大脑皮层运动诱发电位;电镜观察脊髓髓鞘修复及再生情况。结果:各组脊髓神经功能均有不同程度恢复。联合组动物后肢功能恢复显著,BBB评分与其他3组比较差异存在;联合组皮层运动诱发电位的潜伏期缩短、波幅增高,与其他3组比较差异存在。电镜观察,联合组髓鞘松散程度明显减轻,结构规整,线粒体肿胀减轻,薄髓的再生纤维明显增多。结论:脐血干细胞移植联合督脉电针治疗对脊髓损伤的功能恢复有促进作用。     

脐血间充质干细胞移植修复急性肠缺血再灌注损伤

BACKGROUND:Bone marrow mesenchymal stem cells can repair intestinal ischemia-reperfusion injuny by interfering inflammatory reactions after intestinal ischemia-reperfusion to protect intestinal barrier functions. In recent years, umbilical cord blood mesenchymal stem cells are gradually used as a substitute source of bone marrow mesenchymal stem cells. OBJECTIVE:To investigate the effects of umbilical cord blood mesenchymal stem cells on acute intestinal ischemia-reperfusion injury. METHODS:Umbilical cord blood mesenchymal stem cells were induced, isolated in vitro and tracked by CM-DiI fluorescent labeling. Sixty-three Sprague-Dawley rats were equivalently randomized into three groups: control group received normal saline enema, intestinal ischemia-reperfusion injury group with ethanol diluted trinitro-benzene-sulfonic acid and transplantation group administrated with 1×10¹⁰/L umbilical cord blood mesenchymal stem cell suspension via the tail vein at 1 hour after trinitro-benzene-sulfonic acid modeling. At 3 days after transplantation, colon tissues were removed in each group to observe pathological changes of the intestinal tract by hematoxylin-eosin staining. Besides, expression of leptin mRNA in the colon tissues and cyclooxygenase-2 in the mucosa were detected by RT-PCR and immunohistochemistry method, respectively. RESULTS AND CONCLUSION:Transplanted umbilical cord blood mesenchymal stem cells distributed in the intestinal lymphoid tissue and among glandular epithelial cells, suggesting that these stem cells might be involved in the process of intestinal ischemia-reperfusion injury repair. Compared with the control group, intestinal injury in the injury group was significantly aggravated, and most intestinal epithelial cells shed; and the transplantation group appeared to have significantly reduced intestinal damage and significantly less cell shedding. Expression of leptin mRNA was significantly higher in the injury group than the transplantation group followed by the control group, and there were significant differences among the three groups (P < 0.05). Additionally, expression of cyclooxygenase-2 in the injury group was significantly higher than that in the control group (P < 0.05); compared with the injury group, expression of cyclooxygenase-2 was significantly lower in the transplantation group (P < 0.05). To conclude, leptin and cyclooxygenase-2 may be involved in acute intestinal ischemia-reperfusion injury, and umbilical cord blood mesenchymal stem cell transplantation significantly lessens intestinal ischemia-reperfusion injury, which provides an experimental basis for human treating acute intestinal ischemic injury.     

脐血间充质干细胞移植治疗儿童型脊肌萎缩症1例

背景：国内外已有实验动物和临床应用脐血间充质干细胞移植治疗神经系统遗传性疾病安全、有效的诸多报道。 目的：探讨脐血间充质干细胞移植治疗儿童进行性脊髓性肌肉萎缩症的可行性及效果。 方法：2010-01收治1例确诊为儿童进行性脊髓性肌肉萎缩症患儿,经药物及康复治疗无效,行脐血间充质干细胞移植治疗。移植途径采取首次静脉输注,后3次蛛网膜下腔注入,1次/周,每次细胞数量达(4~6)×10⁷个,4次为1个疗程。治疗前和治疗后半年均需完善神经系统体检、实验室检查、肌酶、FIM评分、肌电图等。 结果与结论：移植6个月与移植前比较,肌酶下降,FIM评分由68分提高到93分,肌电图检查重收缩每10.0 ms所检肌运动单位增加两三个,双下肢肌力增加,生活自理能力改善。随访10个月,患者未出现明显的不良反应。提示脐血间充质干细胞移植治疗该例儿童进行性脊髓性肌肉萎缩症患儿有效,其神经功能恢复明显。     

脐带间充质干细胞移植治疗大鼠脑缺血损伤

背景：对于缺血性脑卒中至今尚无确实有效的药物治疗,干细胞因其具有高度自我更新能力和多向分化潜能,使其重建中枢神经系统结构与功能成为可能。 目的：观察脐带间充质干细胞移植治疗缺血性脑卒中模型鼠的效果及安全性,并探讨其可能机制。 方法：体外分离人脐带间充质干细胞,移植前以BrdU标记。将SD雄性大鼠制作大脑中动脉闭塞模型后随机分为3组：移植组于造模后第7天,移植脐带间充质干细胞到损伤侧纹状体,PBS组给予等量PBS,模型组大鼠不做处理。 结果与结论：①人脐带间充质干细胞移植组大鼠mNSS评分恢复优于模型组(P < 0.05);模型组mNSS评分在损伤后35 d内恢复速度慢于模型组(P < 0.05),至第56天与模型组比较差异无显著性意义(P > 0.05)。②移植组大鼠损伤中心及周围均可见Brdu染色阳性细胞及与 Nestin、微管缔合蛋白2、胶原纤维酸性蛋白、Ⅷ因子、血管内皮生长因子免疫组织化学双染阳性细胞。表明脐带间充质干细胞可以在体外分离培养,移植后能在鼠宿主脑内存活、分化,促进大脑中动脉闭塞模型鼠神经功能的恢复。推测其机制可能与移植后细胞分化为神经元样和神经胶质细胞样细胞,并分泌或促进宿主分泌神经营养因子、促进新生血管形成有关。关键词：大脑中动脉闭塞;人脐带间充质干细胞;大鼠;胶原纤维酸性蛋白;血管内皮生长因子;神经功能 doi:10.3969/j.issn.1673-8225.2012.19.011