Therapeutic effects of human adipose stem cell-conditioned medium on stroke
Therapeutic effects of human adipose stem cell-conditioned medium on stroke
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DOI：
10.1002/jnr.23063
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发表时间：
2012-09-01
影响因子：
4.2
通讯作者：
Joo, Kyeung Min
中科院分区：
文献类型：
--
作者：
Cho, Yu Jin;Song, Hyeon Suk;Joo, Kyeung Min
干细胞治疗是一种很有前途的治疗中风的方法。然而，移植细胞的低存活率和潜在的致瘤性可能会破坏细胞治疗的效果。使用干细胞条件培养基（CM）可能是克服这些限制的可行方法。特别是在特定的干细胞培养条件下，CM持续输注缺血性脑，治疗效果更好。将人脂肪干细胞培养成三维球形，以增加血管生成/神经保护因子的分泌。采用标准大脑中动脉闭塞法诱导8周龄sd大鼠脑缺血。术后8天开始向侧脑室持续输注CM或aMEM培养基（0.5 μ l/hr），并维持7天。通过旋转杆试验监测运动功能的改变。术后15 d观察梗死体积、微血管或tunel阳性神经细胞数量。与aMEM相比，连续CM输注可减少梗死面积，维持运动功能。半暗区cd31阳性微血管和tunel阳性神经细胞数量分别显著增加和减少。虽然所有神经细胞类型的凋亡都有所减少，但小胶质细胞凋亡和星形胶质细胞形成的减少是显著的。本研究在动物模型中证实了CM对脑卒中的治疗作用。内皮细胞增殖增加，神经细胞凋亡减少，星形胶质增生减轻可能是影响CM治疗效果的重要因素。(c) 2012 Wiley期刊有限公司
Stem cell therapy is a promising approach for stroke. However, low survival rates and potential tumorigenicity of implanted cells could undermine the efficacy of the cell-based treatment. The use of stem cell-conditioned medium (CM) may be a feasible approach to overcome these limitations. Especially, specific stem cell culture condition and continuous infusion of CM into ischemic brains would have better therapeutic results. The CM was prepared by culturing human adipose-derived stem cells in a three-dimensional spheroid form to increase the secretion of angiogenic/neuroprotective factors. Ischemic stroke was induced by standard middle cerebral artery occlusion methods in the brain of 8-week-old Sprague-Dawley rats. Continuous infusion of CM or aMEM media (0.5 mu l/hr) into the lateral ventricle was initiated 8 days after the surgery and maintained for 7 days. Alteration in the motor function was monitored by the rotarod test. Infarction volume and the number of microvessels or TUNEL-positive neural cells were analyzed 15 days after the surgery. Compared with aMEM, continuous CM infusion reduced the infarction volume and maintained motor function. The number of CD31-positive microvessels and TUNEL-positive neural cells significantly increased and decreased, respectively, in the penumbra regions. Although the apoptosis of all neural cell types decreased, reduction in the microglial apoptosis and astrogliosis was prominent and significant. In this study, the therapeutic effects of the CM against stroke were confirmed in an animal model. Increased endothelial cell proliferation, reduced neural cell apoptosis, and milder astrogliosis may play important roles in the treatment effects of CM. (c) 2012 Wiley Periodicals, Inc.