Augestad Ingrid Lovise, Nyman Axel Karl Gottfrid, Costa Alex Ignatius, Barnett Susan Carol, Sandvig Axel, Håberg Asta Kristine, Sandvig Ioanna
Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Circulation and Medical Imaging, Faculty of Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Neurochem Res. 2017 Jun;42(6):1599-1609. doi: 10.1007/s11064-016-2098-3. Epub 2017 Jan 24.
Effective transplant-mediated repair of ischemic brain lesions entails extensive tissue remodeling, especially in the ischemic core. Neural stem cells (NSCs) are promising reparative candidates for stroke induced lesions, however, their survival and integration with the host-tissue post-transplantation is poor. In this study, we address this challenge by testing whether co-grafting of NSCs with olfactory ensheathing cells (OECs), a special type of glia with proven neuroprotective, immunomodulatory, and angiogenic effects, can promote graft survival and host tissue remodelling. Transient focal cerebral ischemia was induced in adult rats by a 60-min middle cerebral artery occlusion (MCAo) followed by reperfusion. Ischemic lesions were verified by neurological testing and magnetic resonance imaging. Transplantation into the globus pallidus of NSCs alone or in combination with OECs was performed at two weeks post-MCAo, followed by histological analyses at three weeks post-transplantation. We found evidence of extensive vascular remodelling in the ischemic core as well as evidence of NSC motility away from the graft and into the infarct border in severely lesioned animals co-grafted with OECs. These findings support a possible role of OECs as part of an in situ tissue engineering paradigm for transplant mediated repair of ischemic brain lesions.
有效的移植介导的缺血性脑损伤修复需要广泛的组织重塑，尤其是在缺血核心区域。神经干细胞（NSCs）是中风诱导损伤的有前景的修复候选者，然而，它们在移植后的存活以及与宿主组织的整合情况较差。在本研究中，我们通过测试神经干细胞与嗅鞘细胞（OECs）共移植是否能促进移植存活和宿主组织重塑来应对这一挑战，嗅鞘细胞是一种具有已证实的神经保护、免疫调节和血管生成作用的特殊类型神经胶质细胞。通过60分钟大脑中动脉闭塞（MCAo）随后再灌注在成年大鼠中诱导短暂性局灶性脑缺血。通过神经学测试和磁共振成像验证缺血性损伤。在MCAo后两周将单独的神经干细胞或与嗅鞘细胞联合移植到苍白球，然后在移植后三周进行组织学分析。我们在严重损伤的动物中发现，与嗅鞘细胞共移植时，缺血核心区域有广泛血管重塑的证据，以及神经干细胞从移植物向梗死边界移动的证据。这些发现支持嗅鞘细胞作为原位组织工程范式的一部分在移植介导的缺血性脑损伤修复中可能发挥的作用。
