Department of Pediatric Surgery, University of Texas Medical School at Houston, and Children's Memorial Hermann Hospital, University of Texas, Houston, Texas 77030, USA.
Neurosurgery. 2011 Mar;68(3):588-600. doi: 10.1227/NEU.0b013e318207734c.
Severe traumatic brain injury (TBI) in children is associated with substantial long-term morbidity and mortality. Currently, there are no successful neuroprotective/neuroreparative treatments for TBI. Numerous preclinical studies suggest that bone marrow-derived mononuclear cells (BMMNCs), their derivative cells (marrow stromal cells), or similar cells (umbilical cord blood cells) offer neuroprotection.
To determine whether autologous BMMNCs are a safe treatment for severe TBI in children.
Ten children aged 5 to 14 years with a postresuscitation Glasgow Coma Scale of 5 to 8 were treated with 6×10 autologous BMMNCs/kg body weight delivered intravenously within 48 hours after TBI. To determine the safety of the procedure, systemic and cerebral hemodynamics were monitored during bone marrow harvest; infusion-related toxicity was determined by pediatric logistic organ dysfunction (PELOD) scores, hepatic enzymes, Murray lung injury scores, and renal function. Conventional magnetic resonance imaging (cMRI) data were obtained at 1 and 6 months postinjury, as were neuropsychological and functional outcome measures.
All patients survived. There were no episodes of harvest-related depression of systemic or cerebral hemodynamics. There was no detectable infusion-related toxicity as determined by PELOD score, hepatic enzymes, Murray lung injury scores, or renal function. cMRI imaging comparing gray matter, white matter, and CSF volumes showed no reduction from 1 to 6 months postinjury. Dichotomized Glasgow Outcome Score at 6 months showed 70% with good outcomes and 30% with moderate to severe disability.
Bone marrow harvest and intravenous mononuclear cell infusion as treatment for severe TBI in children is logistically feasible and safe.
儿童严重创伤性脑损伤(TBI)与大量的长期发病率和死亡率有关。目前,TBI 没有成功的神经保护/神经修复治疗方法。大量的临床前研究表明,骨髓来源的单核细胞(BMMNCs)、其衍生细胞(骨髓基质细胞)或类似细胞(脐带血细胞)具有神经保护作用。
确定自体 BMMNC 是否是儿童严重 TBI 的安全治疗方法。
10 名年龄在 5 至 14 岁之间、复苏后格拉斯哥昏迷量表评分为 5 至 8 分的儿童,在 TBI 后 48 小时内接受 6×10 个自体 BMMNC/kg 体重的静脉内输注。为了确定该程序的安全性,在骨髓采集期间监测全身和脑血流动力学;通过儿科逻辑器官功能障碍(PELOD)评分、肝酶、Murray 肺损伤评分和肾功能来确定输注相关毒性。在损伤后 1 个月和 6 个月获得常规磁共振成像(cMRI)数据,并进行神经心理学和功能预后评估。
所有患者均存活。无采集相关的全身或脑血流动力学抑制的情况发生。通过 PELOD 评分、肝酶、Murray 肺损伤评分或肾功能,未检测到可察觉的输注相关毒性。比较灰质、白质和 CSF 容积的 cMRI 成像显示,损伤后 1 个月至 6 个月无容积减少。6 个月时的二分 Glasgow 预后评分显示,70%的患者预后良好,30%的患者存在中重度残疾。
对于儿童严重 TBI,骨髓采集和静脉内单核细胞输注作为治疗方法在操作上是可行且安全的。