Kang Mino, Min Kyunghoon, Jang Joonyoung, Kim Seung Chan, Kang Myung Seo, Jang Su Jin, Lee Ji Young, Kim Sang Heum, Kim Moon Kyu, An SeongSoo A, Kim MinYoung
1 Department of Bionanotechnology, Gachon Medical Research Institute, Gachon University , Seongnam, Republic of Korea.
2 Department of Rehabilitation Medicine, CHA Bundang Medical Center, CHA University , Seongnam, Republic of Korea.
Stem Cells Dev. 2015 Oct 1;24(19):2259-68. doi: 10.1089/scd.2015.0074. Epub 2015 Jul 2.
This study evaluated the efficacy of umbilical cord blood (UCB) cell for patients with cerebral palsy (CP) in a randomized, placebo-controlled, double-blind trial and also assessed factors and mechanisms related to the efficacy. Thirty-six children (ages 6 months to 20 years old) with CP were enrolled and treated with UCB or a placebo. Muscle strength and gross motor function were evaluated at baseline and 1, 3, and 6 months after treatment. Along with function measurements, each subject underwent (18)F-fluorodeoxyglucose positron emission tomography at baseline and 2 weeks after treatment. Cytokine and receptor levels were quantitated in serial blood samples. The UCB group showed greater improvements in muscle strength than the controls at 1 (0.94 vs. -0.35, respectively) and 3 months (2.71 vs. 0.65) after treatment (Ps<0.05). The UCB group also showed greater improvements in gross motor performance than the control group at 6 months (8.54 vs. 2.60) after treatment (P<0.01). Additionally, positron emission tomography scans revealed decreased periventricular inflammation in patients administered UCB, compared with those treated with a placebo. Correlating with enhanced gross motor function, elevations in plasma pentraxin 3 and interleukin-8 levels were observed for up to 12 days after treatment in the UCB group. Meanwhile, increases in blood cells expressing Toll-like receptor 4 were noted at 1 day after treatment in the UCB group, and they were correlated with increased muscle strength at 3 months post-treatment. In this trial, treatment with UCB alone improved motor outcomes and induced systemic immune reactions and anti-inflammatory changes in the brain. Generally, motor outcomes were positively correlated with the number of UCB cells administered: a higher number of cells resulted in better outcomes. Nevertheless, future trials are needed to confirm the long-term efficacy of UCB therapy, as the follow-up duration of the present trial was short.
本研究在一项随机、安慰剂对照、双盲试验中评估了脐带血细胞对脑瘫(CP)患者的疗效,并评估了与疗效相关的因素和机制。36名6个月至20岁的CP患儿入组,接受脐带血或安慰剂治疗。在基线以及治疗后1、3和6个月评估肌肉力量和粗大运动功能。除功能测量外,每位受试者在基线和治疗后2周接受(18)F-氟脱氧葡萄糖正电子发射断层扫描。对系列血样中的细胞因子和受体水平进行定量。脐带血组在治疗后1个月(分别为0.94对-0.35)和3个月(2.71对0.65)时肌肉力量的改善比对照组更大(P<0.05)。脐带血组在治疗后6个月(8.54对2.60)时粗大运动表现的改善也比对照组更大(P<0.01)。此外,正电子发射断层扫描显示,与接受安慰剂治疗的患者相比,接受脐带血治疗的患者脑室周围炎症减轻。与粗大运动功能增强相关,脐带血组在治疗后长达12天观察到血浆五聚体3和白细胞介素-8水平升高。同时,脐带血组在治疗后1天观察到表达Toll样受体4的血细胞增加,且它们与治疗后3个月肌肉力量增加相关。在本试验中,单独使用脐带血治疗改善了运动结局,并诱导了全身免疫反应和大脑中的抗炎变化。一般来说,运动结局与所给予的脐带血细胞数量呈正相关:细胞数量越多,结局越好。然而,由于本试验的随访时间较短,未来需要进行试验以确认脐带血治疗的长期疗效。