Department of Histology and Embryology, Akdeniz University School of Medicine, Antalya, Turkey.
Antalya Research and Training Hospital, Neurology Clinic, Antalya, Turkey.
Int J Neurosci. 2022 Mar;132(3):258-268. doi: 10.1080/00207454.2020.1807978. Epub 2020 Aug 24.
Reduction of blood flow below a threshold value in brain regions locally or globally is called cerebral ischemia and proper treatment requires either the restoration of normal blood flow and/or the administration of neuroprotective therapies. Human trophoblast progenitor cells (hTPCs) give rise to the placenta and are responsible for the invasion and vascular remodeling of the maternal vessels within the uterus. Here, we tested whether hTPCs promoted to differentiate along neural lineages may exhibit therapeutic properties in the setting of cerebral ischemia .
Cerebral ischemia was generated in rats middle cerebral artery occlusion and, after 24 h, hTPCs were injected systemically tail vein. Animals were sacrified at Day 3 or 11.
TTC staining indicated that infarct volumes were smaller in hTPC treated animals. Visible myelin recovery was observed in the hTPC injected group with Luxol Fast Blue staining. On Day 11 after hTPC transplantation, DLX5 and VEGF expression, as well as 2 and 10 d after hTPC transplantation, NKX2.2 were significantly increased; while LHX6, Olig1, PDGFRα, VEGFR1 and VEGFR2 showed trends toward improved expression in brain tissue immunoblot analysis. Neuron-like differentiated cells were positive for both NeuN and Cresyl Violet staining.
Here, we demonstrate for the first time that hTPCs enhance the expression of angiogenic and neurogenic factors in rat brain after stroke. Transplantation of hTPCs could form the basis of novel therapeutic approaches for the treatment of stroke in the clinical setting.
脑区局部或整体血流减少至阈值以下称为脑缺血，适当的治疗需要恢复正常血流和/或给予神经保护治疗。人滋养层祖细胞（hTPCs）产生胎盘，并负责子宫内母体血管的侵袭和血管重塑。在这里，我们测试了 hTPC 沿着神经谱系分化是否可以在脑缺血的情况下表现出治疗特性。
通过大脑中动脉闭塞在大鼠中产生脑缺血，并且在 24 小时后，通过尾静脉系统注射 hTPC。动物在第 3 天或第 11 天被处死。
TTC 染色表明 hTPC 处理的动物的梗死体积较小。用 Luxol Fast Blue 染色观察到 hTPC 注射组的可见髓鞘恢复。在 hTPC 移植后的第 11 天，DLX5 和 VEGF 的表达明显增加，而在 hTPC 移植后的第 2 天和第 10 天，NKX2.2 增加；而 LHX6、Olig1、PDGFRα、VEGFR1 和 VEGFR2 在脑组织免疫印迹分析中也表现出改善表达的趋势。神经元样分化细胞对 NeuN 和 Cresyl Violet 染色均呈阳性。
在这里，我们首次证明 hTPCs 在脑卒中后增强大鼠大脑中血管生成和神经发生因子的表达。hTPC 的移植可以为脑卒中的临床治疗提供新的治疗方法的基础。
