Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
J Transl Med. 2010 Jun 28;8:63. doi: 10.1186/1479-5876-8-63.
The therapeutic effect of adipose-derived mesenchymal stem cells (ADMSCs) on brain infarction area (BIA) and neurological status in a rat model of acute ischemic stroke (IS) was investigated.
Adult male Sprague-Dawley (SD) rats (n = 30) were divided into IS plus intra-venous 1 mL saline (at 0, 12 and 24 h after IS induction) (control group) and IS plus intra-venous ADMSCs (2.0 x 106) (treated interval as controls) (treatment group) after occlusion of distal left internal carotid artery. The rats were sacrificed and brain tissues were harvested on day 21 after the procedure.
The results showed that BIA was larger in control group than in treatment group (p < 0.001). The sensorimotor functional test (Corner test) identified a higher frequency of turning movement to left in control group than in treatment group (p < 0.05). mRNA expressions of Bax, caspase 3, interleukin (IL)-18, toll-like receptor-4 and plasminogen activator inhibitor-1 were higher, whereas Bcl-2 and IL-8/Gro were lower in control group than in treatment group (all p < 0.05). Western blot demonstrated a lower CXCR4 and stromal-cell derived factor-1 (SDF-1) in control group than in treatment group (all p < 0.01). Immunohistofluorescent staining showed lower expressions of CXCR4, SDF-1, von Willebran factor and doublecortin, whereas the number of apoptotic nuclei on TUNEL assay was higher in control group than in treatment group (all p < 0.001). Immunohistochemical staining showed that cellular proliferation and number of small vessels were lower but glial fibrillary acid protein was higher in control group than in treatment group (all p < 0.01).
ADMSC therapy significantly limited BIA and improved sensorimotor dysfunction after acute IS.
研究脂肪间充质干细胞(ADMSCs)对急性缺血性脑卒中(IS)大鼠模型脑梗死面积(BIA)和神经状态的治疗作用。
成年雄性 Sprague-Dawley(SD)大鼠(n = 30)分为 IS 后静脉注射 1 mL 生理盐水(IS 诱导后 0、12 和 24 h)(对照组)和 IS 后静脉注射 ADMSCs(2.0 x 106)(治疗间隔与对照组相同)(治疗组)。手术后第 21 天处死大鼠并采集脑组织。
结果显示,对照组 BIA 大于治疗组(p < 0.001)。感觉运动功能测试(Corner 测试)发现对照组转向左侧的频率高于治疗组(p < 0.05)。对照组 Bax、caspase 3、白细胞介素(IL)-18、Toll 样受体-4 和纤溶酶原激活物抑制剂-1 的 mRNA 表达较高,而 Bcl-2 和 IL-8/Gro 较低(均 p < 0.05)。Western blot 显示对照组 CXCR4 和基质细胞衍生因子-1(SDF-1)低于治疗组(均 p < 0.01)。免疫荧光染色显示对照组 CXCR4、SDF-1、von Willebran 因子和双皮质素的表达较低,而 TUNEL 检测到的凋亡核数较高(均 p < 0.001)。免疫组织化学染色显示对照组细胞增殖和小血管数量较低,但胶质纤维酸性蛋白较高(均 p < 0.01)。
ADMSC 治疗可显著缩小急性 IS 后的 BIA,并改善感觉运动功能障碍。