Shin Dong Hoon, Kim Gyu-Hee, Lee Jin Soo, Joo In Soo, Suh-Kim Haeyoung, Kim Sung-Soo, Hong Ji Man
Department of Neurology, Gachon University Gil Hospital, Incheon, 21565, Republic of Korea.
Department of Anatomy, Ajou University School of Medicine, Suwon, 16499, Republic of Korea.
Transl Neurosci. 2016 Dec 30;7(1):164-172. doi: 10.1515/tnsci-2016-0024. eCollection 2016.
Intracerebral (IC) grafting of mesenchymal stem cells (MSCs) is not currently used in humans due to its potential complications. On the other hand, intra-arterial (IA) administration can be facilitated for engrafting of intensifed MSCs in the injured human brain. The study is designed to compare the two methods of MSC administration using IA and IC routes through the parameters of behavior, infarct volume, cell distribution, and MSC identification. An ischemic stroke model was generated in Sprague Dawley male rats. This experiment used MSCs/Ngn1 that express Neurogenin1 (Ngn1) to ensure grafted MSC maintenance. MSCs/Ngn1 or normal saline was administrated via the IC or IA route on day 3. All animals were randomly assigned into four groups (five rats in each group): IC-control, IA-control, IC-MSCs/Ngn1, or IA-MSCs/Ngn1. Motor behaviors, infarct volume, and distribution of superparamagnetic iron oxide (SPIO)-labeled cells on magnetic resonance imaging (MRI) were compared from each group. There were no baseline differencess in motor behaviors or infarct volume between IC-MSCs/Ngn1 and IA-MSCs/Ngn1. Hovever, the IA-MSCs/Ngn1 group showed the greatest recovery on Rotarod testing and adhesive removal tests (p = 0.003 and p = 0.009 vs. IC-MSCs/Ngn1, respectively). The IA-MSCs/Ngn1 group also had more evenly distributed SPIO-labeled cells on MRI. The results suggest that IA administration is likely to be benefcial for humans based on its ability to improve behavioral outcomes and ensure even MSC engrafting.
由于存在潜在并发症，间充质干细胞（MSC）的脑内（IC）移植目前尚未应用于人类。另一方面，动脉内（IA）给药便于强化的MSC植入受伤的人脑。本研究旨在通过行为、梗死体积、细胞分布和MSC鉴定等参数，比较IA和IC途径两种MSC给药方法。在雄性Sprague Dawley大鼠中建立缺血性中风模型。本实验使用表达神经生成素1（Ngn1）的MSC/Ngn1来确保移植的MSC存活。在第3天通过IC或IA途径给予MSC/Ngn1或生理盐水。所有动物随机分为四组（每组五只大鼠）：IC-对照组、IA-对照组、IC-MSC/Ngn1组或IA-MSC/Ngn1组。比较每组的运动行为、梗死体积以及磁共振成像（MRI）上超顺磁性氧化铁（SPIO）标记细胞的分布。IC-MSC/Ngn1组和IA-MSC/Ngn1组在运动行为或梗死体积方面没有基线差异。然而，IA-MSC/Ngn1组在转棒试验和黏附去除试验中显示出最大程度的恢复（分别与IC-MSC/Ngn1组相比，p = 0.003和p = 0.009）。IA-MSC/Ngn1组在MRI上SPIO标记细胞的分布也更均匀。结果表明，基于IA给药改善行为结果和确保MSC均匀植入的能力，其可能对人类有益。
