Intravenously Transplanted Human Bone Marrow Endothelial Progenitor Cells Engraft Within Brain Capillaries, Preserve Mitochondrial Morphology, and Display Pinocytotic Activity Toward Blood-Brain Barrier Repair in Ischemic Stroke Rats.
Intravenously Transplanted Human Bone Marrow Endothelial Progenitor Cells Engraft Within Brain Capillaries, Preserve Mitochondrial Morphology, and Display Pinocytotic Activity Toward Blood-Brain Barrier Repair in Ischemic Stroke Rats.
复制标题
DOI：
10.1002/stem.2578
复制
发表时间：
2017-05
期刊：
影响因子：
--
通讯作者：
Borlongan CV
中科院分区：
文献类型：
--
作者：
Garbuzova-Davis S;Haller E;Lin R;Borlongan CV
中风是一种威胁生命的疾病，治疗选择有限。细胞疗法已经成为一种实验性的中风治疗方法。血脑屏障(BBB)损害是缺血性卒中的重要病理表现，而屏障修复是卒中神经修复的创新靶点。在此，我们通过电子显微镜观察了移植的人骨髓内皮祖细胞对成年SD大鼠大脑中动脉短暂性闭塞(TMCAO)后血脑屏障的修复能力。β-半乳糖苷酶标记的hBMEPC于TMCAO后48h静脉移植。非移植卒中大鼠的微血管超微结构分析显示典型的血脑屏障病变。移植hBMEPC后5天，卒中大鼠双侧纹状体和运动皮质出现广泛的血管修复，以毛细血管内细胞植入为特征。HBMEPC移植的卒中大鼠表现出接近正常的内皮细胞、周细胞和星形胶质细胞的形态，没有检测到血管周围水肿。移植卒中大鼠血管内皮细胞和血管周围星形胶质细胞中也检测到接近正常形态的线粒体。同样值得注意的是，我们在移植细胞中观察到了大量的胞饮小泡。移植的hBMEPC具有强大的植入性和复杂的功能，可能消除了卒中改变的血管系统。在基于细胞的治疗中，保护线粒体和增强胞饮作用代表了卒中血脑屏障修复的一种新的神经恢复机制。
Stroke is a life threatening disease with limited therapeutic options. Cell therapy has emerged as an experimental stroke treatment. Blood-brain barrier (BBB) impairment is a key pathological manifestation of ischemic stroke, and barrier repair is an innovative target for neurorestoration in stroke. Here, we evaluated via electron microscopy the ability of transplanted human bone marrow endothelial progenitor cells (hBMEPCs) to repair the BBB in adult Sprague-Dawley rats subjected to transient middle cerebral artery occlusion (tMCAO). β-galactosidase pre-labeled hBMEPCs were intravenously transplanted 48 hours post-tMCAO. Ultrastructural analysis of microvessels in non-transplant stroke rats revealed typical BBB pathology. At 5 days post-transplantation with hBMEPCs, stroke rats displayed widespread vascular repair in bilateral striatum and motor cortex, characterized by robust cell engraftment within capillaries. hBMEPC transplanted stroke rats exhibited near normal morphology of endothelial cells, pericytes, and astrocytes, without detectable perivascular edema. Near normal morphology of mitochondria was also detected in endothelial cells and perivascular astrocytes from transplanted stroke rats. Equally notable, we observed numerous pinocytic vesicles within engrafted cells. Robust engraftment and intricate functionality of transplanted hBMEPCs likely abrogated stroke-altered vasculature. Preserving mitochondria and augmenting pinocytosis in cell-based therapeutics represent a new neurorestorative mechanism in BBB repair for stroke.