Neuroscience and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, La Paz University Hospital, Hospital La Paz Institute for Health Research (IdiPAZ), Autonomous University of Madrid, Paseo de la Castellana 261, 28046, Madrid, Spain.
Biomarkers and Therapeutic Targets Unit, Instituto Ramón y Cajal de investigación Sanitaria (IRYCIS), Madrid, Spain.
Stem Cell Res Ther. 2020 Feb 19;11(1):70. doi: 10.1186/s13287-020-01601-1.
Mesenchymal stem cell-derived extracellular vesicles (EVs) are one of the most promising therapeutics in protective and/or regenerative therapy in animal models of stroke using a dose of 100 μg. However, whether EVs dose is related to outcomes is not known. This study aimed to identify the optimal effective dose of EVs from adipose tissue-derived mesenchymal stem cells that promote functional recovery in subcortical stroke.
For this purpose, various doses of EVs were tested in an in vitro oxygen-glucose deprivation (OGD) model of oligodendrocytes and neuronal ischemia. At least 50 μg of EVs were necessary to induce proliferation and differentiation of oligodendrocyte and neurons in OGD conditions. For in vivo study, rats were subjected to subcortical stroke and various doses (50 μg, 100 μg, or 200 μg) of EVs were intravenously administered after 24 h.
All the animals in the EV groups showed significant improvement in functional tests, with an increase in tract connectivity and brain repair-associated markers, and a decrease in cell death and in astrocyte-marker expression. Cell proliferation was increased in the groups receiving 50 μg and 100 μg doses. Only the 50-μg dose was associated with significant increases in brain-derived neurotrophic factor expression.
In conclusion, 50 μg of EVs appears to be the minimal effective dose to enhance protection, brain repair, and recovery in subcortical ischemic stroke.
间充质干细胞衍生的细胞外囊泡（EVs）是在皮质下卒中动物模型中使用 100μg 剂量进行保护和/或再生治疗最有前途的治疗方法之一。然而，EVs 剂量是否与结果相关尚不清楚。本研究旨在确定脂肪组织来源的间充质干细胞衍生的 EVs 的最佳有效剂量，以促进皮质下卒中后的功能恢复。
为此，在体外氧葡萄糖剥夺（OGD）寡突胶质细胞和神经元缺血模型中测试了各种剂量的 EVs。至少需要 50μg 的 EVs 才能在 OGD 条件下诱导少突胶质细胞和神经元的增殖和分化。在体内研究中，大鼠接受皮质下卒中，在 24 小时后静脉给予 50μg、100μg 或 200μg 不同剂量的 EVs。
所有 EV 组的动物在功能测试中均表现出显著改善，轴突连接和与脑修复相关的标志物增加，细胞死亡和星形胶质细胞标志物表达减少。接受 50μg 和 100μg 剂量的细胞增殖增加。只有 50μg 剂量与脑源性神经营养因子表达的显著增加相关。
总之，50μg 的 EVs 似乎是增强皮质下缺血性卒中保护、脑修复和恢复的最小有效剂量。
