Marcus Center for Cellular Cures, Duke University School of Medicine, Durham, NC, USA.
Department of Physical and Occupational Therapy, Duke University School of Medicine, Durham, NC, USA.
Dev Med Child Neurol. 2022 Dec;64(12):1477-1486. doi: 10.1111/dmcn.15325. Epub 2022 Jul 10.
To evaluate safety and motor function after treatment with allogeneic umbilical cord blood (AlloCB) or umbilical cord tissue-derived mesenchymal stromal cells (hCT-MSC) in children with cerebral palsy (CP).
Ninety-one children (52 males, 39 females; median age 3 years 7 months [range 2-5 years]) with CP due to hypoxic-ischemic encephalopathy, stroke, or periventricular leukomalacia were randomized to three arms: (1) the AlloCB group received 10 × 10 AlloCB total nucleated cells (TNC) per kilogram at baseline (n = 31); (2) the hCT-MSC group received 2 × 10 hCT-MSC at baseline, 3 months, and 6 months (n = 28); (3) the natural history control group received 10 × 10 AlloCB TNC per kilogram at 12 months (n = 31). Motor function was assessed with the Gross Motor Function Measure-66 (GMFM-66) and Peabody Developmental Motor Scale, Second Edition.
Infusions (n = 143) were well tolerated, with eight infusion reactions (three in the AlloCB group, five in hCT-MSC) and no other safety concerns. At 12 months, the mean differences (95% confidence intervals [CI]) between actual and expected changes in GMFM-66 score were AlloCB 5.8 points (3.4-8.2), hCT-MSC 4.3 (2.2-6.4), and natural history 3.1 (1.4-5.0). In exploratory, post hoc analysis, the mean GMFM-66 score (95% CI) of the hCT-MSC group was 1.4 points higher than natural history (-1.1 to 4.0; p = 0.27), and the AlloCB group was 3.3 points higher than natural history (0.59-5.93; p = 0.02) after adjustment for baseline Gross Motor Function Classification System level, GMFM-66 score, and etiology.
High-dose AlloCB is a potential cell therapy for CP and should be further tested in a randomized, blinded, placebo-controlled trial.
Unrelated donor allogeneic umbilical cord blood (AlloCB) and human umbilical cord tissue-derived mesenchymal stromal cell infusion is safe in young children with cerebral palsy. Significant changes in motor function were not observed 6 months after treatment. One year later, treatment with AlloCB was associated with greater increases in Gross Motor Function Measure-66 scores.
评估异体脐带血（AlloCB）或脐带组织来源间充质基质细胞（hCT-MSC）治疗脑瘫患儿的安全性和运动功能。
91 名脑瘫患儿（男 52 例，女 39 例；中位年龄 3 岁 7 个月[范围 2-5 岁]）因缺氧缺血性脑病、中风或脑室周围白质软化症接受治疗，随机分为三组：（1）AlloCB 组在基线时接受 10×10 个/kg 的异体脐带血总核细胞（TNC）（n=31）；（2）hCT-MSC 组在基线时、3 个月和 6 个月时接受 2×10 hCT-MSC（n=28）；（3）自然史对照组在 12 个月时接受 10×10 个/kg 的异体脐带血 TNC（n=31）。采用粗大运动功能测量-66 量表（GMFM-66）和 Peabody 发育运动量表第二版评估运动功能。
输注（n=143）耐受良好，发生 8 例输注反应（AlloCB 组 3 例，hCT-MSC 组 5 例），无其他安全性问题。12 个月时，GMFM-66 评分实际与预期变化的平均差值（95%置信区间[CI]）为 AlloCB 组 5.8 分（3.4-8.2），hCT-MSC 组 4.3 分（2.2-6.4），自然史组 3.1 分（1.4-5.0）。在探索性的事后分析中，hCT-MSC 组的 GMFM-66 评分（95%CI）比自然史组高 1.4 分（-1.1 至 4.0；p=0.27），AlloCB 组比自然史组高 3.3 分（0.59-5.93；p=0.02），校正基线粗大运动功能分类系统水平、GMFM-66 评分和病因后。
异基因脐带血（AlloCB）是脑瘫患儿潜在的细胞治疗方法，应在随机、盲法、安慰剂对照试验中进一步测试。
未配对的异体脐带血（AlloCB）和人脐带组织来源的间充质基质细胞输注在脑瘫的幼儿中是安全的。治疗后 6 个月未观察到运动功能的显著变化。一年后，AlloCB 治疗与 GMFM-66 评分的更大增加相关。
