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一名完全性脊髓损伤患者多次间充质干细胞移植后的持续改善

Continuous improvement after multiple mesenchymal stem cell transplantations in a patient with complete spinal cord injury.

作者信息

Jarocha Danuta, Milczarek Olga, Wedrychowicz Anna, Kwiatkowski Stanislaw, Majka Marcin

机构信息

Department of Transplantation, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Cracow, Poland.

出版信息

Cell Transplant. 2015;24(4):661-72. doi: 10.3727/096368915X687796. Epub 2015 Mar 24.

Abstract

Interruption of spinal cord (SC) continuity leads to functional loss below the lesion level. The purpose of this study was to evaluate the safety and efficacy of bone marrow nucleated cell (BMNC) and multiple mesenchymal stem cell (MSC) transplantations in spinal cord injury (SCI). A patient with total SC interruption at the Th2-3 level underwent experimental therapy with BMNC and MSC transplantations followed with intensive neurorehabilitation treatment. At admission, 6 h after SCI, the patient was scored ASIA A, had a Th1 sensation level, paraplegia with sphincter palsy, and was without the ability to control trunk movement. Neurophysiology examination showed bilateral axonal damage to the motor and sensory neural fibers with no motor unit potentials or peripheral motor nerve conduction in the lower extremities. The standard therapy had been applied and had not produced any positive results. The patient was treated with autologous BMNCs injected intravenously (3.2×10(9)) and intrathecally (0.5×10(9)) 10 weeks after the SCI and with five rounds of MSCs every 3-4 months (1.3-3.65×10(7)) administered via lumbar puncture. Total number of transplanted MSC cells during the course of treatment was 1.54×10(8). There were no complications related to transplantations and no side effects related to the therapy during 2 years of treatment. The ASIA score improved from A to C/D (from 112 to 231 points). The sensation level expanded from Th1 to L3-4, and the patient's ability to control the body trunk was fully restored. Bladder filling sensation, bladder control, and anal sensation were also restored. Muscle strength in the left lower extremities improved from plegia to deep paresis (1 on the Lovett scale). The patient's ability to move lower extremities against gravity supported by the movements in quadriceps was restored. The patient gained the ability to stand in a standing frame and was able to walk with the support of hip and knee ortheses. Magnetic resonance imaging (MRI) revealed that at the Th2/Th3 level, where the hemorrhagic necrosis was initially observed, small tissue structures appeared. Our results suggest that repeated intrathecal infusions of MSCs might have the potential to produce clinically meaningful improvements for SCI patients.

摘要

脊髓(SC)连续性中断会导致损伤平面以下功能丧失。本研究旨在评估骨髓有核细胞(BMNC)和多能间充质干细胞(MSC)移植治疗脊髓损伤(SCI)的安全性和有效性。一名胸2 - 3水平脊髓完全中断的患者接受了BMNC和MSC移植的实验性治疗,随后进行了强化神经康复治疗。入院时,SCI后6小时,患者美国脊髓损伤协会(ASIA)分级为A级,感觉平面为胸1,截瘫伴括约肌麻痹,无法控制躯干运动。神经生理学检查显示双侧运动和感觉神经纤维轴突损伤,下肢无运动单位电位或周围运动神经传导。已应用标准治疗但未产生任何积极效果。该患者在SCI后10周接受了静脉注射自体BMNC(3.2×10⁹)和鞘内注射(0.5×10⁹),并每3 - 4个月通过腰椎穿刺给予五轮MSC(1.3 - 3.65×10⁷)。治疗过程中移植的MSC细胞总数为1.54×10⁸。在2年的治疗期间,未出现与移植相关的并发症,也未出现与治疗相关的副作用。ASIA评分从A级提高到C/D级(从112分提高到231分)。感觉平面从胸1扩展到腰3 - 4,患者控制躯干的能力完全恢复。膀胱充盈感觉、膀胱控制和肛门感觉也恢复了。左下肢肌力从瘫痪改善为重度轻瘫(Lovett分级为1级)。患者获得了在站立架上站立的能力,并能够在髋部和膝部矫形器的支撑下行走。磁共振成像(MRI)显示,在最初观察到出血性坏死的胸2/胸3水平出现了小组织结构。我们的结果表明,重复鞘内输注MSC可能有潜力为SCI患者带来具有临床意义的改善。

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