Therapeutic benefit of intracerebral transplantation of bone marrow stromal cells after cerebral ischemia in rats
Therapeutic benefit of intracerebral transplantation of bone marrow stromal cells after cerebral ischemia in rats
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DOI：
10.1016/s0022-510x(01)00557-3
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发表时间：
2001-08-15
影响因子：
4.4
通讯作者：
Chopp, M
中科院分区：
文献类型：
--
作者：
Chen, JL;Li, Y;Chopp, M
我们验证了大脑中动脉闭塞（MCAo）后，骨髓基质细胞（MSCs）移植到缺血边界区后存活、分化并促进功能恢复的假设。从成年大鼠身上获取间充质干细胞，分别在添加或不添加神经生长因子（NGF）的情况下培养。为了进行细胞鉴定，用溴脱氧尿苷（BrdU）预标记MSCs。24只大鼠给予MCAo 2 h， 24 h接受移植物移植，MCAo 14 d后安乐死。试验组包括：(1)对照组- mcao单独组（n = 8）；(2) MSCs脑内移植（n = 8）；(3) NGF培养的MSCs脑内移植（n = 8）。采用免疫组织化学方法鉴定骨髓间充质干细胞。在MCAo前后分别进行行为测试（rottarod，粘连去除和改良神经严重程度评分[NSS]）。这些数据表明MSCs能够存活、迁移并分化为表型神经细胞。与对照组相比，移植MSCs的动物体感觉行为恢复显著（p < 0.05）， NSS恢复显著（p < 0.05）。与对照组相比，接受NGF培养的MSCs在运动（p < 0.05）、体感（p < 0.05）和NSS （p < 0.05）行为测试中均有显著恢复。我们的数据表明，脑内骨髓间充质干细胞移植可能为中风提供一种强大的自体成形术治疗。(C) 2001 Elsevier Science B.V.版权所有
We tested the hypothesis that bone marrow stromal cells (MSCs) transplanted into the ischemic boundary zone, survive, differentiate and improve functional recovery after middle cerebral artery occlusion (MCAo). MSCs were harvested from adult rats and cultured with or without nerve growth factor (NGF). For cellular identification, MSCs were prelabeled with bromodeoxyuridine (BrdU). Rats (n = 24) were subjected to 2 h of MCAo, received grafts at 24 h and were euthanized at 14 days after MCAo. Test groups consisted of: (1) control-MCAo alone (n = 8); (2) intracerebral transplantation of MSCs (n = 8); (3) intracerebral transplantation of MSCs cultured with NGF (n = 8). Immunohistochemistry was used to identify cells from MSCs. Behavioral tests (rotarod, adhesive-removal and modified neurological severity score [NSS]) were performed before and after MCAo. The data demonstrate that MSCs survive, migrate and differentiate into phenotypic neural cells. Significant recovery of somatosensory behavior (p < 0.05) and NSS (p < 0.05) were found in animals transplanted with MSCs compared with control animals. Animals that received MSCs cultured with NGF displayed significant recovery in motor (p < 0.05), somatosensory (p < 0.05) and NSS (p < 0.05) behavioral tests compared with control animals. Our data suggest that intracerebral transplantation of MSCs may provide a powerful autoplastic therapy for stroke. (C) 2001 Elsevier Science B.V. All rights reserved.