大鼠实验性蛛网膜下腔出血后静脉移植间充质干细胞的治疗益处。

Therapeutic benefit of intravenous transplantation of mesenchymal stem cells after experimental subarachnoid hemorrhage in rats.

机构信息

Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

出版信息

J Stroke Cerebrovasc Dis. 2012 Aug;21(6):445-51. doi: 10.1016/j.jstrokecerebrovasdis.2010.10.005. Epub 2011 Feb 1.

DOI:10.1016/j.jstrokecerebrovasdis.2010.10.005

PMID:21282068

Abstract

BACKGROUND

Subarachnoid hemorrhage (SAH) usually occurs when an aneurysm ruptures and bleeds into the subarachnoid space. However, no information is available regarding the therapeutic potency of transplanted mesenchymal stem cells (MSCs) for SAH. Therefore, our aim was to investigate whether MSC transplantation therapy may cause stem cell activation and improve neurologic functional recovery after induction of SAH.

METHODS

Female rats were divided into 2 groups of SAH plus phosphate-buffered saline (PBS; control) and SAH plus MSCs (experimental). Both control and experimental groups received PBS or injection of 3 × 10(6) male rat MSCs labeled with bromodeoxyuridine (BrdU) into the tail vein 24 hours after SAH. All animals were killed 14 days after SAH. A behavioral test (Neurological Severity Score) was performed at 1, 7, and 14 days after SAH. Immunohistochemistry was used to identify MSCs and the cells derived from MSCs in brains with SAH. Terminal deoxynucleotidyltransferase mediated dUTP-biotin nick-end labeling was used to identify apoptotic cells.

RESULTS

Significant functional recovery (P < .05) was found in SAH animals infused with MSCs compared with other rats. Significantly more BrdU-positive cells were located in the parietal lobe of MSC-treated than in PBS-treated animals. MSCs were also seen to differentiate into glial cells (GFAP), neurons (Neu-N), and endothelial cells (vWF), thereby enhancing neuroplastic effects in the injured brain. Significantly fewer apoptotic cells were found in insulted cerebral tissue in SAH plus MSC rats when compared with other groups.

CONCLUSIONS

Intravenously transplanted MSCs improve functional recovery, reduce apoptosis, and enhance neuroplastic effects after SAH in animal models. This is a promising novel procedure to repair central nervous system damage after SAH, and may provide a new way to induce plasticity in the injured brain cells.

摘要

背景

蛛网膜下腔出血（SAH）通常是由于动脉瘤破裂并出血到蛛网膜下腔而发生的。然而，目前尚无关于移植间充质干细胞（MSCs）治疗 SAH 的疗效信息。因此，我们的目的是研究 MSC 移植治疗是否可以引起干细胞激活并改善 SAH 后的神经功能恢复。

方法

将雌性大鼠分为蛛网膜下腔出血加磷酸盐缓冲盐水（PBS；对照组）和蛛网膜下腔出血加 MSCs（实验组）两组。对照组和实验组均在 SAH 后 24 小时通过尾静脉注射 3×10(6)雄性大鼠标记有溴脱氧尿苷（BrdU）的 MSCs。所有动物均在 SAH 后 14 天处死。在 SAH 后 1、7 和 14 天进行行为测试（神经严重程度评分）。免疫组织化学用于鉴定 SAH 脑内的 MSC 和 MSC 衍生细胞。末端脱氧核苷酸转移酶介导的 dUTP-生物素缺口末端标记法用于鉴定凋亡细胞。

结果

与其他大鼠相比，接受 MSC 输注的 SAH 动物的功能恢复明显（P<.05）。在 MSC 治疗的动物中，BrdU 阳性细胞明显更多地位于顶叶。还发现 MSC 分化为神经胶质细胞（GFAP）、神经元（Neu-N）和内皮细胞（vWF），从而增强了损伤大脑的神经可塑性。与其他组相比，SAH 加 MSC 大鼠损伤脑组织中的凋亡细胞明显减少。