Department of Neurology, Tokai University School of Medicine, Isehara, Japan.
Department of Physiology, Tokai University School of Medicine, Isehara, Japan.
PLoS One. 2019 Jan 25;14(1):e0210198. doi: 10.1371/journal.pone.0210198. eCollection 2019.
Various cell-based therapeutic strategies have been investigated for vascular and tissue regeneration after ischemic stroke. We have developed a novel cell population, called regeneration-associated cells (RACs), by quality- and quantity-controlled culture of unfractionated mononuclear cells. RACs were trans-arterially injected into 10-week-old syngeneic male mice at 1, 3, 5 or 7 days after permanent middle cerebral artery occlusion (MCAO) to determine the optimal timing for administration in terms of outcome at day 21. Next, we examined the effects of RACs injection at day 1 after MCAO on neurological deficits, infarct volume, and mediators of vascular regeneration and anti-inflammation at days 7 and 21. Infarct volume at day 21 was significantly reduced by transplantation of RACs at day 1 or 3. RACs injected at day 1 reduced the infarct volume at day 7 and 21. Angiogenesis and anti-inflammatory mediators, VEGF and IL-10, were increased at day 7, and VEGF was still upregulated at day 21. We also observed significantly enhanced ink perfusion in vivo, tube formation in vitro, and definitive endothelial progenitor cell colonies in colony assay. These results suggest that RAC transplantation in MCAO models promoted significant recovery of neural tissues through intensified anti-inflammatory and angiogenic effects.
各种基于细胞的治疗策略已被用于缺血性中风后的血管和组织再生。我们通过对未分离的单核细胞进行质量和数量控制培养，开发了一种新的细胞群体，称为再生相关细胞（RACs）。RACs 在永久性大脑中动脉闭塞（MCAO）后 1、3、5 或 7 天通过动脉内注射到 10 周龄同基因雄性小鼠中，以确定在第 21 天的结果方面进行管理的最佳时机。接下来，我们研究了在 MCAO 后第 1 天注射 RACs 对神经功能缺损、梗死体积以及血管再生和抗炎介质的影响，分别在第 7 天和第 21 天进行检测。在第 1 天或第 3 天进行 RACs 移植可显著减小第 21 天的梗死体积。在第 1 天注射的 RACs 可减小第 7 天和第 21 天的梗死体积。在第 7 天，血管生成和抗炎介质 VEGF 和 IL-10 增加，在第 21 天 VEGF 仍上调。我们还观察到体内墨水灌注明显增强，体外管形成和集落分析中明确的内皮祖细胞集落。这些结果表明，在 MCAO 模型中移植 RAC 可通过增强抗炎和血管生成作用促进神经组织的显著恢复。
