Liem Nguyen Thanh, Chinh Vu Duy, Phuong Dam Thi Minh, Van Doan Ngo, Forsyth Nicholas R, Heke Michael, Thi Phuong Anh Nguyen, Nguyen Xuan-Hung
Vinmec Research Institute of Stem Cell and Gene Technology (VRISG), Vinmec Health Care System, Hanoi, Vietnam.
College of Health Sciences, VinUniversity, Hanoi, Vietnam.
Front Pediatr. 2020 Sep 10;8:564. doi: 10.3389/fped.2020.00564. eCollection 2020.
Anoxic brain injury (ABI) due to non-fatal drowning may cause persistent vegetative state (VS) that is currently incurable. The aim of this paper is to present the safety and feasibility of autologous bone marrow-derived mononuclear cell (BMMNC) transplantation in five drowning children surviving in persistent VS. We used BMMNC as a novel candidate therapeutic tool in a pilot phase-I study for five patients affected by neurological sequelae after near-death drowning. Autologous BMMNCs were freshly isolated using Ficoll gradient centrifugation then infused intrathecally to five patients. The number of transplantation varied from two to four times depending on the motor function improvement of patient after transplantation. Clinical therapeutic effects were evaluated using gross motor function measure and muscle spasticity rating scales, cognitive assessments, and brain MRI before and after cell administrations. Six months after BMMNC transplantation, no serious complications or adverse events were reported. All five patients displayed improvement across the major parameters of gross motor function, cognition, and muscle spasticity. Three patients displayed improved communication including the expression of words. In particular, one patient remarkably reduced cerebral atrophy, with nearly normal cerebral parenchyma after BMMNC transplantation. Autologous BMMNC transplantation for the treatment of children in persistent VS after drowning is safe, feasible, and can potentially improve motor function and cognition and reduce muscle spasticity. These results pave the way for a future phase II clinical trial to evaluate the efficacy of the therapy.
非致命性溺水导致的缺氧性脑损伤（ABI）可能会引发目前无法治愈的持续性植物状态（VS）。本文旨在介绍自体骨髓来源的单个核细胞（BMMNC）移植在五名持续性VS状态下存活的溺水儿童中的安全性和可行性。在一项针对五名濒死溺水后出现神经后遗症患者的I期试验性研究中，我们将BMMNC作为一种新型候选治疗工具。使用Ficoll梯度离心法新鲜分离自体BMMNC，然后将其鞘内注入五名患者体内。根据患者移植后运动功能的改善情况，移植次数从两次到四次不等。在细胞给药前后，使用粗大运动功能测量和肌肉痉挛评定量表、认知评估以及脑部MRI对临床治疗效果进行评估。BMMNC移植六个月后，未报告严重并发症或不良事件。所有五名患者在粗大运动功能、认知和肌肉痉挛等主要参数方面均有改善。三名患者的沟通能力有所提高，包括言语表达。特别是，一名患者的脑萎缩明显减轻，BMMNC移植后脑实质几乎恢复正常。自体BMMNC移植治疗溺水后持续性VS状态的儿童是安全、可行的，并且有可能改善运动功能和认知能力，减轻肌肉痉挛。这些结果为未来评估该疗法疗效的II期临床试验铺平了道路。
