CD14 monocytes promote the immunosuppressive effect of human umbilical cord matrix stem cells

Here, the effect of CD14⁺ monocytes on human umbilical cord matrix stem cell (hUC-MSC)-mediated immunosuppression was studied in vitro. hUC-MSCs exerted a potent inhibitory effect on the proliferation and interferon-γ (IFN-γ) secretion capacities of CD4⁺ and CD8⁺ T cells in response to anti-CD3/CD28 stimulation. Transwell co-culture system revealed that the suppressive effect was primarily mediated by soluble factors. Addition of prostaglandin synthesis inhibitors (indomethacin or NS-398) almost completely abrogated the immunosuppression activity of hUC-MSCs, identifying prostaglandin E₂ (PGE₂) as an important soluble mediator. CD14⁺ monocytes were found to be able to enhance significantly the immunosuppressive effect of hUC-MSCs in a dose-dependent fashion. Moreover, the inflammatory cytokine IL-1β, either exogenously added or produced by CD14⁺ monocytes in culture, could trigger expression of high levels of PGE₂ by hUC-MSCs, whereas inclusion of the IL-1 receptor antagonist (IL-1RA) in the culture down-regulated not only PGE₂ expression, but also reversed the promotional effect of CD14⁺ monocytes and partially restored CD4⁺ and CD8⁺ T cell proliferation and IFN-γ secretion. Our data demonstrate an important role of monocytes in the hUC-MSC-induced immunomodulation, which may have important implications in future efforts to explore the clinical potentials of hUC-MSCs.     

Efficacy of mesenchymal stromal cells intraspinal transplantation for patients with different degrees of spinal cord injury: A systematic review and meta-analysis

Background aimsSeveral studies have reported that mesenchymal stromal cells (MSCs) may improve neurological functions in patients with spinal cord injury (SCI). In this study, we conducted a systematic review and meta-analysis to summarize the effects of MSC treatment on different degrees of severity of SCI.MethodsSystematic searching of studies reporting outcomes of MSCs on specific injury severities of patients with SCI was performed in The National Library of Medicine (MEDLINE), Embase and Cochrane for published articles up to the 6 July 2022. Two investigators independently reviewed the included studies and extracted the relevant data. The standardized mean differences of American Spinal Injury Association (ASIA) motor score, ASIA light touch scores, ASIA pinprick scores and the Barthel index between baseline and follow-ups were pooled.ResultsA total of eight studies were included. A large majority focused on patients with ASIA grade A classification. The pooled mean differences of ASIA motor scores, ASIA light touch scores, ASIA pinprick scores and the Barthel index were –2.78 (95% confidence interval [CI] –5.12 to –0.43, P = 0.02), –18.26 (95% CI –26.09 to –10.43, P < 0.01), –17.08 (95% CI –24.10 to –10.07, P < 0.01) and –4.37 (95% CI –10.96 to 2.22, P = 0.19), respectively.ConclusionsMSC transplantation was a significantly effective therapy for patients with SCI with ASIA grade A. In the future, further studies are warranted to confirm the potential beneficial effects of MSC therapy.     

人脐带间充质干细胞对脊柱骨折大鼠愈合及神经功能的影响

摘要 目的：探讨人脐带间充质干细胞(Human umbilical cord mesenchymal stem cells,hUC-MSCs)对脊柱骨折大鼠愈合及神经功能的影响。方法：脊柱骨折Sprague-Dawley雄性大鼠模型30只随机分为hUC-MSCs组与对照组,各15只。hUC-MSCs组大鼠在骨折部位移植0.5 mL的hUC-MSCs(细胞浓度为2×10⁶/mL),对照组大鼠移植同体积的生理盐水,记录大鼠愈合及神经功能变化情况。结果：两组造模后15 min、30 min、90 min的平均动脉压都波动明显,不过组间对比差异无统计学意义(P>0.05)。与造模后2 w对比,两组造模后4 w的神经功能BBB评分均升高,且hUC-MSCs组造模后2 w、4 w的神经功能BBB评分都高于对照组(P<0.05)。hUC-MSCs组造模后8 w的骨体积分数高于对照组(P<0.05)。hUC-MSCs组骨折部位附近有少量骨痂生长,骨折线逐渐消失;骨痂已明显包裹骨折部位。hUC-MSCs组造模后8 w的脊髓细胞凋亡指数低于对照组(P<0.05)。结论：hUC-MSCs在脊柱骨折大鼠的应用能促进骨折愈合与改善神经功能,也可以抑制脊髓细胞凋亡,从而发挥很好的治疗作用。     

Long-term cultured mesenchymal stem cells frequently develop genomic mutations but do not undergo malignant transformation

Cultured human umbilical cord mesenchymal stem cells (hUC-MSCs) are being tested in several clinical trials and encouraging outcomes have been observed. To determine whether in vitro expansion influences the genomic stability of hUC-MSCs, we maintained nine hUC-MSC clones in long-term culture and comparatively analyzed them at early and late passages. All of the clones senesced in culture, exhibiting decreased telomerase activity and shortened telomeres. Two clones showed no DNA copy number variations (CNVs) at passage 30 (P30). Seven clones had ≥1 CNVs at P30 compared with P3, and one of these clones appeared trisomic chromosome 10 at the late passage. No tumor developed in immunodeficient mice injected with hUC-MSCs, regardless of whether the cells had CNVs at the late passage. mRNA-Seq analysis indicated that pathways of cell cycle control and DNA damage response were downregulated during in vitro culture in hUC-MSC clones that showed genomic instability, but the same pathways were upregulated in the clones with good genomic stability. These results demonstrated that hUC-MSCs can be cultured for many passages and attain a large number of cells, but most of the cultured hUC-MSCs develop genomic alterations. Although hUC-MSCs with genomic alterations do not undergo malignant transformation, periodic genomic monitoring and donor management focusing on genomic stability are recommended before these cells are used for clinical applications.     

Current evidence on mesenchymal stem cell therapy for traumatic spinal cord injury: systematic review and meta-analysis

Background aimsThe authors aim to analyze the evidence in the literature regarding the efficacy and safety of mesenchymal stem cell (MSC) therapy in human subjects with traumatic spinal cord injury (SCI) and identify its potential role in the management of SCI.MethodsThe authors conducted independent and duplicate searches of electronic databases, including PubMed, Embase and the Cochrane Library, until May 2020 for studies analyzing the efficacy and safety of stem cell therapy for SCI. American Spine Injury Association (ASIA) impairment scale (AIS) grade improvement, ASIA sensorimotor score, activities of daily living score, residual urine volume, bladder function improvement, somatosensory evoked potential (SSEP) improvement and adverse reactions were the outcomes analyzed. Analysis was performed in R platform using OpenMeta[Analyst] software.ResultsNineteen studies involving 670 patients were included for analysis. On analysis, the intervention group showed statistically significant improvement in AIS grade (P < 0.001), ASIA sensory score (P < 0.017), light touch (P < 0.001), pinprick (P = 0.046), bladder function (P = 0.012), residual urine volume (P = 0.023) and SSEP (P = 0.002). However, no significant difference was noted in motor score (P = 0.193) or activities of daily living score (P = 0.161). Although the intervention group had a significant increase in complications (P < 0.001), no serious or permanent adverse events were reported. On subgroup analysis, low concentration of MSCs (<5 × 10⁷ cells) and initial AIS grade A presentation showed significantly better outcomes than their counterparts.ConclusionsThe authors’ analysis establishes the efficacy and safety of MSC transplantation in terms of improvement in AIS grade, ASIA sensory score, bladder function and electrophysiological parameters like SSEP compared with controls, without major adverse events. However, further research is needed to standardize dose, timing, route and source of MSCs used for transplantation.     

Suppression of Cholangiocarcinoma Cell Growth by Human Umbilical Cord Mesenchymal Stem Cells: A Possible Role of Wnt and Akt Signaling

Emerging evidence indicates that human mesenchymal stem cells (hMSCs) can be recruited to tumor sites, and affect the growth of human malignancies. However, little is known about the underlying molecular mechanisms. Here, we observed the effects of hMSCs on the human cholangiocarcinoma cell line, HCCC-9810, using an animal transplantation model, and conditioned media from human umbilical cord-derived mesenchymal stem cells (hUC-MSCs). Animal studies showed that hUC-MSCs can inhibit the growth of cholangiocarcinoma xenograft tumors. In cell culture, conditioned media from hUC-MSCs inhibited proliferation and induced apoptosis of tumor cells in a dose- and time-dependent manner. The proliferation inhibition rate increased from 6.21% to 49.86%, whereas the apoptosis rate increased from 9.3% to 48.1% when HCCC-9810 cells were cultured with 50% hUC-MSC conditioned media for 24 h. Immunoblot analysis showed that the expression of phosphor-PDK1 (Ser241), phosphor-Akt (Ser 437 and Thr308), phosphorylated glycogen synthase kinase 3β (phospho-GSK-3β^Ser9), β-catenin, cyclin-D1, and c-myc were down-regulated. We further demonstrated that CHIR99021, a GSK-3β inhibitor reversed the suppressive effects of hUC-MSCs on HCCC-9810 cells and increased the expression of β-catenin. The GSK-3β activator, sodium nitroprusside dehydrate (SNP), augmented the anti-tumor effects of hUC-MSCs and decreased the expression of β-catenin. IGF-1 acted as an Akt activator, and also reversed the suppressive effects of hUC-MSCs on HCCC-9810 cells. All these results suggest that hUC-MSCs could inhibit the malignant phenotype of HCCC-9810 human cholangiocarcinoma cell line. The cross-talk role of Wnt/β-catenin and PI3K/Akt signaling pathway, with GSK-3β as the key enzyme bridging these pathways, may contribute to the inhibition of cholangiocarcinoma cells by hUC-MSCs.     

Conditioned medium from umbilical cord mesenchymal stem cells improves nasal mucosa damage by radiation

Objectives

To explore therapeutic effects of conditioned medium from human umbilical cord mesenchymal stem cells (hUC-MSCs) on nasal mucosa radiation damage both in vivo and in vitro.

Results

The mucus cilia clearance time (7 and 30 days), degree of mucosal edema (7, 30, 90 and 180 days), cilia coverage (180 days) of concentrated conditioned medium group improved compared with radiotherapy control group. The proliferation and migration abilities of irradiated and non-irradiated nasal epithelial cells significantly increased after culture in bronchial epithelial cell growth medium (BEGM) containing 10% conditioned medium of hUC-MSCs compared to cells cultured in BEGM alone.

Conclusions

Soluble factors secreted by hUC-MSCs may promote nasal epithelial cell proliferation and migration. Intranasal administration of hUC-MSC conditioned medium effectively repairs nasal mucosa radiation damage.

     

Neural differentiation of umbilical cord mesenchymal stem cells by sub-sonic vibration

AimsAdult stem cells, such as umbilical cord-derived mesenchymal stem cells (UC-MSCs), have the potential to differentiate into various types of cells, including neurons. Research has shown that mechanical stimulation induces a response in MSCs, specifically, low and high intensity sub-sonic vibration (SSV) has been shown to facilitate wound healing. In this study, the effects of SSV were examined by assessing the proliferation and differentiation properties of MSCs.Main methodshUC-MSCs were isolated from Wharton's jelly, including the smooth muscle layer of the umbilical cord. During subculture, the cells were passaged every 5–6 days using nonhematopoietic stem cell media. To measure the effect of sonic vibration, SSV was applied to these cells continuously for 5 days.Key findingsIn this study, the morphology of hUC-MSCs was altered to resemble neurons by SSV. Further, the mRNA and protein levels of neuron-specific markers, including MAP2, NF-L, and NeuroD1, increased. In addition, other neural cell markers, such as GFAP and O4, were increased. These results suggest that hUC-MSCs differentiated into neural cells upon SSV nonselectively. In a mechanism study, the ERK level increased in a time-dependent manner upon SSV for 12 h.SignificanceThe results of this study suggest that SSV caused hUC-MSCs to differentiate into neural cells via ERK activation.     

Cotransplantation of human umbilical cord-derived mesenchymal stem cells and umbilical cord blood-derived CD34+ cells in a rabbit model of myocardial infarction

The objective of the study is to investigate the effect of hypoxic preconditioning on the immunomodulatory properties of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and the effect of cotransplantation of hUC-MSCs and human umbilical cord blood (hUCB)-derived CD34⁺ cells in a rabbit model of myocardial infarction. hUC-MSCs with or without hypoxic preconditioning by cobalt chloride were plated in a 24-well plate, and then cocultured with hUCB-CD34⁺ cells and PBMCs for 96 h at 37 °C in a 5 % CO₂ incubator. For the negative control, hUC-MSCs were omitted. The groups were divided as follows: A1 = HP-MSCs + hUCB-CD34⁺ cells + PBMC, A2 = hUC-MSCs + hUCB-CD34⁺ cells + PBMC, Negative Control = hUCB-CD34⁺ cells + PBMC. Culture supernatants of each group were collected, and the IL-10 and IFN-γ levels were measured by ELISA. A rabbit model of MI was established using a modified Fujita method. The animals were then randomized into three groups and received intramyocardial injections of 0.4 ml of PBS alone (n = 8, PBS group), hUC-MSCs in PBS (n = 8, hUC-MSCs group), or hUC-MSCs + CD34⁺ cells in PBS (n = 8, Cotrans group), at four points in the infarct border zone. Echocardiography was performed at baseline, 4 weeks after MI induction, and 4 weeks after cell transplantation, respectively. Stem cell differentiation and neovascularization in the infracted area were characterized for the presence of cardiac Troponin I (cTnI) and CD31 by immunohistochemical staining, and the extent of myocardial fibrosis was evaluated by hematoxylin and eosin (H&E) and Masson’s trichrome. IFN-γ was 27.00 ± 1.11, 14.20 ± 0.81, and 7.22 ± 0.14 pg/ml, and IL-10 was 31.68 ± 3.08, 61.42 ± 1.08, and 85.85 ± 1.80 pg/ml for the Control, A1 and A2 groups, respectively, which indicated that hUCB-CD34⁺ cells induced immune reaction of peripheral blood mononuclear cells, whereas both hUC-MSCs and HP-MSCs showed an immunosuppressive effect, which, however, was attenuated by hypoxic preconditioning. The Cotrans group had less collagen deposition in the infarcted myocardium and better heart function than the hUC-MSCs or PBS group. The presence of cTnI-positive cells and CD31-positive tubular structures indicated the differentiation of stem cells into cardiomyocytes and neovascularization. The microvessel density was 12.19 ± 3.05/HP for the hUC-MSCs group and 31.63 ± 2.45/HP for the Cotrans group, respectively (P < 0.01). As a conclusion, both hUC-MSCs and HP-MSCs have an immunosuppressive effect on lymphocytes, which, however, can be attenuated by hypoxic preconditioning. Cotransplantation of hUC-MSCs and hUCB-CD34⁺ cells can improve heart function and decrease collagen deposition in post-MI rabbits. Thus, a combined regimen of hUC-MSCs and hUCB-CD34⁺ cells would be more desirable than either cells administered alone. This is most likely due to the increase of cardiomyocytes and enhanced angiogenesis in the infarcted myocardium.     

Intrathecal administration of autologous mesenchymal stromal cells for spinal cord injury: Safety and efficacy of the 100/3 guideline

Background aims

Cell therapy with autologous mesenchymal stromal cells (MSCs) in patients with spinal cord injury (SCI) is beginning, and the search for its better clinical application is an urgent need.

温针灸联合中药湿热敷治疗脑中风后肢体痉挛的疗效及对患者肢体运动、日常活动能力的影响

目的:研究温针灸联合中药湿热敷治疗脑中风后肢体痉挛的疗效及对患者肢体运动、日常活动功能的影响。方法:选取2017年3月到2018年4月在长春中医药大学附属医院接受脑中风后肢体痉挛治疗患者60例,按照随机数字表法将所有患者分为观察组和对照组各30例,对照组在常规处理的基础上给予温针灸治疗,观察组在对照组的基础上给予中药湿热敷治疗,采用改良Ashworth量表对比患者治疗前后肢体痉挛改善程度,通过Barthel指数评分对比患者治疗前后的日常活动能力,采用Fugl-Meyer评分对两组患者肢体运动能力进行评定。结果:两组治疗15 d和治疗30 d后的上、下肢体痉挛评分与治疗前比较均明显降低,Fugl-Meyer评分与治疗前比较均明显升高(P0.05),且治疗30 d后Fugl-Meyer评分与治疗15 d比较明显升高(P0.05)。治疗15 d、治疗30 d后,观察组上、下肢体痉挛评分均明显低于对照组,Fugl-Meyer评分均高于对照组(P0.05)。两组治疗30 d后Barthel指数评分较治疗前均有上升,且观察组评分显著高于对照组(P0.05)。结论:温针灸联合中药湿热敷治疗对脑中风后肢体痉挛有较好的疗效,能有效恢复患者脑中风后肢体运动功能,改善患者日常活动能力。     

In vivo magnetic resonance imaging tracking of SPIO-labeled human umbilical cord mesenchymal stem cells

Human umbilical cord mesenchymal stem cells (hUC-MSCs) can be efficiently labeled by superparamagnetic iron oxide (SPIO) nanoparticles, which produces low signal intensity on magnetic resonance imaging (MRI) in vitro. This study was to evaluate the feasibility of in vivo tracking for hUC-MSCs labeled by SPIO with noninvasive MRI. SPIO was added to cultures at concentrations equivalent to 0, 7, 14, 28, and 56 μg Fe/ml (diluted with DMEM/F12) and incubated for 16 h. Prussian Blue staining was used to determinate the labeling efficiency. Rats were randomly divided into three groups, control group, hUC-MSCs group, and SPIO-labeled hUC-MSCs group. All groups were subjected to spinal cord injury (SCI) by weight drop device. Rats were examined for neurological function. In vivo MRI was used to track SPIO-labeled hUC-MSCs transplanted in rats spinal cord. Survival and migration of hUC-MSCs were also explored using immunofluorescence. Significant improvements in locomotion were observed in the hUC-MSCs groups. There was statistical significance compared with control group. In vivo MRI 1 and 3 weeks after injection showed a large reduction in signal intensity in the region transplanted with SPIO-labeled hUC-MSCs. The images from unlabeled hUC-MSCs showed a smaller reduction in signal intensity. Transplanted hUC-MSCs engrafted within the injured rats spinal cord and survived for at least 8 weeks. In conclusion, hUC-MSCs can survive and migrate in the host spinal cord after transplantation, which promote functional recovery after SCI. Noninvasive imaging of transplanted SPIO-labeled hUC-MSCs is feasible.     

二甲双胍对人脐带间充质干细胞形态、增殖、表面标志及细胞周期的影响

目的探讨不同浓度二甲双胍（METF）对人脐带间充质干细胞（hUC-MSC）形态、增殖、表面标志及细胞周期的影响。 方法取健康足月新生儿脐带在体外分离出hUC-MSC进行传代培养,至第3代（流式细胞仪分析）对细胞进行鉴定,取第6代处于对数生长期的hUC-MSC （相对老化）,将对照组与不同浓度METF （0.1,1,5,10,20?mmol/L）干预的细胞进行比较,观察不同浓度METF干预对细胞的形态、增殖率（MTT法分别于24、48、72?h检测）、及细胞表面标志和细胞周期的影响,采用One-Way ANOVA,及LSD-t检验进行统计学分析。 结果（1）METF为0.1?mmol/L、1?mmol/L,细胞形态无显著改变,当药物浓度为5?~?20?mmol/?L时,随着药物浓度增加、培养时间延长,细胞形态改变越显著。（2）METF为0.1?mmol/L（24?h：101.28±0.98,24?h：104.06±1.76,24?h：101.51±0.67）促进hUC-MSC增殖,药物浓度为1?~ 10?mmol/L在培养初期可增加间充质干细胞的增殖率,随着培养时间的延长,细胞的增殖逐渐被抑制。METF为20?mmol/L（24?h：86.64±0.66,48?h：58.38±2.52,72?h：17.75±1.35）抑制细胞增殖,抑制作用随着时间延长而增强（P?< 0.05）。（3）当METF浓度为5,10,20?mmol/L时,随着药物浓度的增加,CD105的表达逐渐减弱（F?= 17.539,P?< 0.05）。METF未对CD44、CD90产生影响。（4）METF为0.1?mmol/L时降低G0/G1期的比例（64.16±1.20,P?< 0.05）,促进间充质干细胞的增殖,随着药物浓度的增加,细胞增殖逐渐被抑制。 结论METF浓度在0.1mmol/?L促进hUC-MSC增殖,而在浓度5 ~ 20?mmol/L时抑制人脐带间充质干细胞的增殖及表面标志CD105的表达,不同浓度的METF均未对CD44、CD90的表达产生影响。     

单倍体相合造血干细胞移植联合脐带间充质干细胞输注治疗儿童重型再生障碍性贫血的临床观察及安全性分析

目的观察单倍体相合造血干细胞移植（hi-HSCT）联合脐带间充质干细胞（hUC-MSC）输注治疗儿童重型再生障碍性贫血（SAA）的临床效果及安全性。 方法整理海军总医院儿科2010年2月至2014年1月收治的11例接受hi-HSCT联合hUC-MSC输注治疗的SAA患儿的临床资料,进行回顾性分析。对其治疗情况、并发症发生情况及生存情况进行观察,总结该治疗方案的临床效果与安全性,以及治疗体会。 结果患儿全部获得造血重建,移植后1个月复查嵌合体均为70% ~ 100%供者嵌合。白细胞植入时间8 ~ 21 d,中位时间为12 d;血小板植入时间10 ~ 24 d,中位时间为15 d。11例患儿中,2例发生Ⅰ度急性移植物抗宿主病（GVHD）,1例发生Ⅲ度急性GVHD,均经相关治疗后好转;1例发生局限性慢性GVHD,经相关治疗后好转;2例发生广泛性慢性GVHD,发生率为18.18%。患儿移植期间均发生不同程度的恶心、呕吐、纳差和发热等症状,给予对症支持治疗后好转。8例（72.73%）发生口腔黏膜炎,2例（18.18%）发生肺部感染,9例（81.82%）发生病毒感染,2例（18.18%）发生腹泻,均经综合治疗后好转。11例患儿随访时间12 ~ 29个月,中位随访时间16个月,截止末次随访时1例因广泛性慢性GVHD接受持续治疗,2例接受免疫抑制剂减量治疗,其余4例均停用免疫抑制剂;1例患儿因家属自行停用环孢素A发生排异死亡。 结论hi-HSCT联合hUC-MSC输注治疗儿童SAA具有良好临床疗效,值得进一步关注。     

人脐带间充质干细胞重复静脉注射动物毒性试验

摘要 目的：评价多次尾静脉注射脐带间充质干细胞（hUC-MSCs）对小鼠的体内毒性作用。方法：48只健康ICR小鼠,按性别和体重随机分为4组（即对照组、低剂量组、中剂量组和高剂量组）。小鼠通过微静脉注射不同剂量hUC-MSCs悬浮液,间隔3天给药1次,共给药4次。记录小鼠摄食量、体重、体温,给药结束后恢复两周后牺牲动物作大体解剖,检查各个器官器质性病变;利用流式细胞仪分别检测CD3、CD4、CD8阳性细胞亚群数量;ELISA试剂盒检测血清IgM、IgG、C3、C4指标;对肺脏、脾脏、肾脏行组织病理学检查。结果：实验组与对照组相比较,注射不同剂量干细胞后一般观察、体重、体温、摄食量、IgM以及C3在给药期和恢复期均未发生显著变化。在恢复期,注射中、高剂量hUC-MSCs组血清IgG和C4水平略有降低,但未达到显著水平P<0.05;CD4阳性T细胞集群数量以及CD4/CD8系数在hUC-MSCs中、高剂量组显著上升（P<0.05）。大体剖检,除脾脏相比溶媒对照组略显增大外其它各器官均未发现肉眼可见明显异常;称重后发现hUC-MSCs高剂量组脾重量与溶媒对照组相比显著升高（P<0.05）。脾脏、肺脏、肾脏病理学检测未见明显异常。结论：健康ICR小鼠尾静脉注射临床剂量hUC-MSCs（1×10⁶ cells/kg）可能调动动物免疫反应,此外,未观察到hUC-MSCs对小鼠有明显毒副作用。     

Efficacy and Safety of Transcutaneous Electrical Acupoint Stimulation to Treat Muscle Spasticity following Brain Injury: A Double-Blinded,Multicenter, Randomized Controlled Trial

ObjectiveThis study was aimed at evaluating the clinical efficacy and safety of transcutaneous electrical acupoint stimulation (TEAS) to treat muscle spasticity after brain injury (Chinese Clinical Trial Registry: ChiCTR-TRC-11001310).MethodsA total of 60 patients with muscle spasticity after brain injury were randomized to the following 3 groups: 100, 2, and 0 Hz (sham) TEAS. The acupoints Hegu (LI4)—Yuji (LU10) and Zusanli (ST36)—Chengshan (BL57) on the injured side were stimulated at 0, 2, or 100 Hz, 5 times per week for 4 weeks. The patients were followed up for 1 and 2 months after the treatments. The effects of the treatments on muscle spasticity at the wrist, thumb, the other 4 fingers, elbow, shoulder, knee, and ankle were evaluated by the Modified Ashworth Scale, and the effects on disability were assessed by the Disability Assessment Scale. The walking capability was evaluated by the Holden functional ambulation classification score. The overall performance was assessed by the Global Assessment Scale score and the improved Barthel Index. The safety of the treatments administered was also monitored.ResultsThe wrist spasticity was significantly reduced from baseline at weeks 2, 3, and 4 of treatment and at the 1- and 2-month follow-up visits in the 100 Hz group (P < 0.01). Compared with 2 Hz or sham TEAS, 100 Hz TEAS decreased wrist spasticity at weeks 2, 3, and 4 of treatment and 1 month after treatment (P < 0.001). The other endpoints were not affected by the treatments. No treatment-emergent adverse events were reported during treatments and follow-up visits.ConclusionsTEAS appears to be a safe and effective therapy to relieve muscle spasticity after brain injury, although large-scale studies are required to further verify the findings.

Trial Registration

Chinese Clinical Trial Registry ChiCTR-TRC-11001310 http://www.chictr.org     

Assessment of post-stroke elbow flexor spasticity in different forearm positions

Abstract

Purpose/Aim: There have been conflicting results regarding which muscle contribute most to the elbow spastic flexion deformity. This study aimed to investigate whether flexor spasticity of the elbow changed according to the position of the forearm, and to determine the muscle or muscles that contributed most to the elbow spastic flexion deformity by clinical examination.

Methods: This study is a single group, observational and cross-sectional study. Sixty patients were assessed for elbow flexor spasticity in different forearm positions (pronation, neutral and supination) with Modified Tardieu Scale. The primary outcome measure was a domain of the Modified Tardieu Scale, the dynamic component of spasticity (spasticity angle).

Results: In general, there was a significant difference between forearm positions regarding spasticity angle (p?<?.001). In pairwise comparisons, median spasticity angles in pronation (70 degrees) and neutral position (60 degrees) were significantly higher than those in supination (57.5 degrees) (adjusted p?<?.001 and adjusted p?=?.003, respectively). However, median spasticity angle in pronation did not differ significantly from those in neutral position in favour of pronation (adjusted p?=?.274).

Conclusions: The severity of spasticity changes according to the elbow position which suggests that the magnitude of contribution of each elbow flexor muscle to spastic elbow deformity is different. Reduction of spasticity from pronation to supination leads us to consider brachialis as the most spastic muscle. Since biceps was suggested to be the least spastic muscle in this study, and also to avoid spastic pronation deformity of the forearm, it should be rethought before performing chemodenervation into biceps muscle.     

Spasticity and spastic dystonia: the two faces of velocity-dependent hypertonia

BackgroundSpasticity and spastic dystonia are two separate phenomena of the upper motor neuron syndrome. Spasticity is clinically defined by velocity-dependent hypertonia and tendon jerk hyperreflexia due to the hyper-excitability of the stretch reflex. Spastic dystonia is the inability to relax a muscle leading to a spontaneous tonic contraction. Both spasticity and spastic dystonia are present in patients who are at rest; however, only patients with spasticity are actually able to kept their muscles relaxed prior to muscle stretch. The idea that has inspired the present work is that also in patients with spastic dystonia the stretch reflex is likely to be hyper-excitable. Therefore, velocity-dependent hypertonia could be mediated not only by spasticity, but also by spastic dystonia.MethodsTonic stretch reflexes in the rectus femoris muscle were evoked in 30 patients with multiple sclerosis showing velocity-dependent hypertonia of leg extensors and the habituation of the reflex was studied. Moreover, the capability of relax the muscle prior to muscle stretch (spastic dystonia) was also investigated.ResultsA tonic stretch reflex was evoked in all the enrolled patients. 73% of the patients were able to relax their rectus femoris muscle prior to stretch (spasticity). In the overwhelming majority of these patients, the tonic stretch reflex decreased during repeated stretches. In the remaining 27% of the subjects, the muscle was tonically activated prior to muscle stretch (spastic dystonia). In the patients in whom spastic dystonia progressively increased over the subsequent stretches (50% of the subjects with spastic dystonia), the habituation of the reflex was replaced by a progressive reflex facilitation.DiscussionThis study shows for the first time that velocity-dependent hypertonia can be caused by two distinct phenomena: spasticity and spastic dystonia. The habituation of the tonic stretch reflex, which is a typical feature of spasticity, is replaced by a reflex facilitation in the half of the subject with spastic dystonia. These preliminary findings suggest that differentiating the two types of velocity-dependent muscle hypertonia (spasticity and spastic dystonia) could be clinically relevant.