Department of Neurosurgery, Anam Hospital, College of Medicine, Korea University, 73 Goryeodae-ro Seongbuk-gu, Seoul, 02841, Republic of Korea.
Department of Biotechnology, College of Life Sciences and Biotechnology, Science Campus, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea.
Tissue Eng Regen Med. 2020 Oct;17(5):695-704. doi: 10.1007/s13770-020-00293-1. Epub 2020 Sep 8.
Mannitol increases blood-brain barrier permeability and can improve the efficiency of systemically administered stem cells by facilitating stem cell entry from the periphery into the injured brain. The aim of this study was to elucidate the neuroprotective effects of a combination of mannitol pretreatment and stem cell transplantation on stroke-induced neural injury.
The experimental rats were randomly assigned to three groups 24 h after middle cerebral artery occlusion and reperfusion. One group received intravenous (IV) injections of phosphate-buffered saline (vehicle), another group received IV injections of human adipose-derived stem cells (hADSCs), and the last group received IV injections of hADSCs 10 min after IV mannitol injections. Neurobehavioral functions and infarct volume were compared. Immunohistochemistry (IHC) analyses were performed using antibodies against ionized calcium binding adapter-1 (IBA-1), rat endothelial antigen-1 (RECA-1), and bromodeoxyuridine/doublecortin (BrdU/DCX).
PKH-26 labeling revealed no difference in the number of stem cells that had migrated into the injured brain, and hADSC transplantation did not improve the infarct volume. However, neurobehavioral functions improved in the mannitol group. IHC showed higher numbers of RECA-1-positive cells in the peri-infarcted brain and BrdU-/DCX-colocalized cells in the subventricular zone in the mannitol group. IBA-1-positive cell number decreased in the hADSC-only and mannitol-pretreatment groups compared with the vehicle group even though there was no difference between the former two groups.
Combinatorial treatment with mannitol and hADSC transplantation may have better therapeutic potential than hADSC monotherapy for ischemic stroke.
甘露醇可增加血脑屏障通透性，通过促进干细胞从外周进入受损的大脑，提高系统给予的干细胞的效率。本研究旨在阐明甘露醇预处理和干细胞移植联合对缺血性卒中诱导的神经损伤的神经保护作用。
大脑中动脉闭塞再灌注后 24 小时，实验大鼠随机分为三组。一组静脉注射磷酸盐缓冲盐水（载体），另一组静脉注射人脂肪源性干细胞（hADSCs），最后一组静脉注射甘露醇 10 分钟后静脉注射 hADSCs。比较神经行为功能和梗死体积。用离子钙结合接头蛋白-1（IBA-1）、大鼠内皮抗原-1（RECA-1）和溴脱氧尿苷/双皮质素（BrdU/DCX）抗体进行免疫组织化学（IHC）分析。
PKH-26 标记显示，进入受损大脑的干细胞数量没有差异，hADSC 移植也没有改善梗死体积。然而，甘露醇组的神经行为功能得到改善。IHC 显示甘露醇组梗死周边区 RECA-1 阳性细胞数量较高，侧脑室下区 BrdU/DCX 共定位细胞数量较高。与载体组相比，hADSC 组和甘露醇预处理组的 IBA-1 阳性细胞数量减少，尽管前两组之间没有差异。
与 hADSC 单一疗法相比，甘露醇联合 hADSC 移植的联合治疗可能对缺血性中风具有更好的治疗潜力。
