PDF(Pubmed)
Abstract：
UNASSIGNED: Cell therapy using neural progenitor cells (NPCs) is a promising approach for ischemic stroke treatment according to the results of multiple preclinical studies in animal stroke models. In the vast majority of conducted animal studies, the therapeutic efficacy of NPCs was estimated after intracerebral transplantation, while the information of the effectiveness of systemic administration is limited. Nowadays, several clinical trials aimed to estimate the safety and efficacy of NPCs transplantation in stroke patients were also conducted. In these studies, NPCs were transplanted intracerebrally in the subacute/chronic phase of stroke. The results of clinical trials confirmed the safety of the approach, however, the degree of functional improvement (the primary efficacy endpoint) was not sufficient in the majority of the studies. Therefore, more studies are needed in order to investigate the optimal transplantation parameters, especially the timing of cell transplantation after the stroke onset. This study aimed to evaluate the therapeutic effects of intra-arterial (IA) and intravenous (IV) administration of NPCs derived from induced pluripotent stem cells (iNPCs) in the acute phase of experimental stroke in rats. Induced pluripotent stem cells were chosen as the source of NPCs as this technology is perspective, has no ethical concerns and provides the access to personalized medicine.
UNASSIGNED: Human iNPCs were transplanted IA or IV into male Wistar rats 24 h after the middle cerebral artery occlusion stroke modeling. Therapeutic efficacy was monitored for 14 days and evaluated in comparison with the cell transplantation-free control group. Additionally, cell distribution in the brain was assessed.
UNASSIGNED: The obtained results show that both routes of systemic transplantation (IV and IA) significantly reduced the mortality and improved the neurological deficit of experimental animals compared to the control group. At the same time, according to the MRI data, only IA administration led to faster and prominent reduction of the stroke volume. After IA administration, iNPCs transiently trapped in the brain and were not detected on day 7 after the transplantation. In case of IV injection, transplanted cells were not visualized in the brain. The obtained data demonstrated that the systemic transplantation of human iNPCs in the acute phase of ischemic stroke can be a promising therapeutic strategy.
UNASSIGNED: Human iNPCs were transplanted IA or IV into male Wistar rats 24 h after the middle cerebral artery occlusion stroke modeling. Therapeutic efficacy was monitored for 14 days and evaluated in comparison with the cell transplantation-free control group. Additionally, cell distribution in the brain was assessed.
UNASSIGNED: The obtained results show that both routes of systemic transplantation (IV and IA) significantly reduced the mortality and improved the neurological deficit of experimental animals compared to the control group. At the same time, according to the MRI data, only IA administration led to faster and prominent reduction of the stroke volume. After IA administration, iNPCs transiently trapped in the brain and were not detected on day 7 after the transplantation. In case of IV injection, transplanted cells were not visualized in the brain. The obtained data demonstrated that the systemic transplantation of human iNPCs in the acute phase of ischemic stroke can be a promising therapeutic strategy.
摘要：
■根据在动物中风模型中进行的多项临床前研究的结果，使用神经祖细胞（NPC）的细胞疗法是一种有前途的缺血性中风治疗方法。在绝大多数进行的动物研究中，NPC的治疗效果在脑内移植后估计，而全身给药有效性的信息有限。如今,我们还进行了几项旨在评估NPCs移植在卒中患者中的安全性和有效性的临床试验.在这些研究中,NPC在中风的亚急性/慢性期进行脑内移植。临床试验结果证实了该方法的安全性,然而,在大多数研究中,功能改善程度(主要疗效终点)不足.因此,需要更多的研究来研究最佳的移植参数，特别是中风发作后细胞移植的时机。这项研究旨在评估动脉内（IA）和静脉内（IV）施用源自诱导多能干细胞（iNPC）的NPC在大鼠实验性中风急性期的治疗效果。选择诱导多能干细胞作为NPCs的来源，因为这项技术的观点，没有道德问题，并提供个性化医疗。
■在大脑中动脉阻塞中风建模后24小时，将人iNPCsIA或IV移植到雄性Wistar大鼠中。监测治疗效果14天，并与无细胞移植对照组进行比较。此外,评估大脑中的细胞分布。
■获得的结果表明，与对照组相比，全身移植的两种途径（IV和IA）均显着降低了死亡率，并改善了实验动物的神经功能缺损。同时,根据核磁共振数据,只有IA给药导致更快、更显著的每搏输出量降低.IA管理后，iNPC暂时捕获在脑中并且在移植后第7天未检测到。在静脉注射的情况下，移植的细胞在大脑中没有可见。获得的数据表明，在缺血性中风的急性期进行人iNPC的全身移植可能是一种有前途的治疗策略。
■在大脑中动脉阻塞中风建模后24小时，将人iNPCsIA或IV移植到雄性Wistar大鼠中。监测治疗效果14天，并与无细胞移植对照组进行比较。此外,评估大脑中的细胞分布。
■获得的结果表明，与对照组相比，全身移植的两种途径（IV和IA）均显着降低了死亡率，并改善了实验动物的神经功能缺损。同时,根据核磁共振数据,只有IA给药导致更快、更显著的每搏输出量降低.IA管理后，iNPC暂时捕获在脑中并且在移植后第7天未检测到。在静脉注射的情况下，移植的细胞在大脑中没有可见。获得的数据表明，在缺血性中风的急性期进行人iNPC的全身移植可能是一种有前途的治疗策略。
