Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
Stem Cell Res Ther. 2020 Jun 5;11(1):219. doi: 10.1186/s13287-020-01739-y.
This study tested the optimal time point for left intra-carotid arterial (LICA) administration of circulatory-derived autologous endothelial progenitor cells (EPCs) for improving the outcome in rat after acute ischemic stroke (IS).
Adult male SD rats (n = 70) were equally categorized into group 1 (sham-operated control), group 2 (IS), group 3 (IS+EPCs/1.2 × 10 cells/by LICA administration 3 h after IS), group 4 (IS+EPCs/LICA administration post-day-3 IS), group 5 (IS+EPCs/LICA administration post-day-7 IS), group 6 (IS+EPCs/LICA administration post-day-14 IS), and group 7 (IS+EPCs/LICA administration post-day-28 IS). The brain infarct volume (BIV) (at day 60/MRI) was lowest in group 1, highest in group 2, and significantly progressively increased from groups 3 to 7, whereas among the IS animals, the neurological function was significantly preserved in groups 3 to 6 than in groups 2 and 7 post-day-60 IS (all P < 0.0001). By day 60, the endothelial cell markers at protein and cellular levels and number of small vessels exhibited an opposite pattern of BIV among the groups (all P < 0.0001). The protein and cellular levels of inflammation, and protein levels of oxidative stress, autophagy, and apoptosis were highest in group 2, lowest in group 1, and progressively increased from groups 3 to 7 (all P < 0.0001). The angiogenesis biomarkers at protein and cellular levels were significantly progressively increased from groups 1 to 3, then significantly progressively decreased from groups 4 to 7 (all P < 0.0001).
Early EPC administration provided better benefits on improving functional/image/molecular-cellular outcomes after acute IS in rat.
本研究旨在探讨经左侧颈内动脉（LICA）输注循环源性自体内皮祖细胞（EPC）改善大鼠急性缺血性脑卒中（IS）后转归的最佳时间点。
将 70 只成年雄性 SD 大鼠等分为 1 组（假手术对照）、2 组（IS）、3 组（IS+EPCs/1.2×10 个细胞，于 IS 后 3 小时通过 LICA 给药）、4 组（IS+EPCs，于 IS 后第 3 天通过 LICA 给药）、5 组（IS+EPCs，于 IS 后第 7 天通过 LICA 给药）、6 组（IS+EPCs，于 IS 后第 14 天通过 LICA 给药）和 7 组（IS+EPCs，于 IS 后第 28 天通过 LICA 给药）。第 60 天/MRI 时，脑梗死体积（BIV）最低的是 1 组，最高的是 2 组，而从 3 组到 7 组则逐渐增加，在 IS 动物中，与第 60 天 IS 后的 2 组和 7 组相比，3 组到 6 组的神经功能明显更能被保留（均 P<0.0001）。第 60 天，各组之间 BIV 的内皮细胞标志物的蛋白和细胞水平以及小血管数量呈相反模式（均 P<0.0001）。炎症的蛋白和细胞水平以及氧化应激、自噬和细胞凋亡的蛋白水平在 2 组中最高，在 1 组中最低，从 3 组到 7 组逐渐增加（均 P<0.0001）。蛋白和细胞水平的血管生成生物标志物从 1 组到 3 组显著逐渐增加，然后从 4 组到 7 组显著逐渐降低（均 P<0.0001）。
大鼠急性 IS 后早期 EPC 给药对改善功能/影像/分子细胞结局具有更好的益处。
