Human amniotic epithelial stem cells inhibit microglia activation through downregulation of tumor necrosis factor-α, interleukin-1β and matrix metalloproteinase-12 in vitro and in a rat model of intracerebral hemorrhage
Human amniotic epithelial stem cells inhibit microglia activation through downregulation of tumor necrosis factor-α, interleukin-1β and matrix metalloproteinase-12 in vitro and in a rat model of intracerebral hemorrhage
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DOI：
10.1016/j.jcyt.2013.11.007
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发表时间：
2014-04-01
期刊：
影响因子：
4.5
通讯作者：
Zhang, Xiangtong
中科院分区：
文献类型：
--
作者：
Liang, Hongsheng;Guan, Dong;Zhang, Xiangtong
背景目标。干细胞移植促进脑出血(ICH)后功能恢复的分子机制尚不清楚。越来越多的证据表明，小胶质细胞在脑出血后不久就被激活，这种激活参与了脑出血引起的继发性脑损伤。我们研究了人羊膜上皮干细胞(HAESCs)对小胶质细胞激活的影响。方法：研究方法。为了研究HAESCs在体外的作用，我们用凝血酶激活小胶质细胞。凝血酶治疗24小时后，采用酶联免疫吸附试验检测血清肿瘤坏死因子-cc和白细胞介素1-β水平。体内移植HAESCs于胶原酶诱导脑出血1d后移植到大鼠纹状体。分别用逆转录聚合酶链式反应和免疫组织化学方法检测脑出血后7d血肿周围组织中基质金属蛋白酶12的表达水平和小胶质细胞的浸润情况。结果。当HAESCs与小胶质细胞共培养时，凝血酶激活的小胶质细胞肿瘤坏死因子-α、白介素1β和基质金属蛋白酶-12的表达通过接触依赖和旁分泌机制显著降低。大鼠脑内移植HAESCs后，血肿周围组织中基质金属蛋白酶-12的表达水平和小胶质细胞的浸润明显减少。结论。我们的观察表明，HAESCs在体内外均能抑制小胶质细胞的激活，这可能是HAESCs移植减轻脑水肿、改善脑出血后神经功能障碍的重要机制之一。因此，我们推测抑制小胶质细胞活化和减轻炎症反应的方法可以用于设计有效的脑出血治疗策略。
Background aims. The molecular mechanisms by which stem cell transplantation improves functional recovery after intracerebral hemorrhage (ICH) are not well understood. Accumulating evidence suggests that microglia cells are activated shortly after ICH and that this activation contributes to secondary ICH-induced brain injury. We studied the effect of human amniotic epithelial stem cells (HAESCs) on microglia activation. Methods. To study the effect of HAESCs in vitro, we used thrombin to activate the microglia cells. Twenty-four hours after thrombin treatment, the levels of tumor necrosis factor-cc and interleukin-1 beta were measured by enzyme-linked immunosorbent assay. In vivo, the HAESCs were transplanted into the rat striatum 1 day after collagenase-induced ICH. The expression levels of matrix metalloproteinase (MMP)-12 and microglia infiltration in the peri-hematoma tissues were determined 7 days after ICH through the use of reverse transcriptase polymerase chain reaction and immunohistochemical analysis, respectively. Results. Thrombin-activated microglia expression of tumor necrosis factor-alpha, interleukin-1 beta and MMP-12 was significantly reduced through contact-dependent and paracrine mechanisms when the HAESCs were co-cultured with microglia cells. After transplantation of HAESCs in rat brains, the expression levels of MMP-12 and microglia infiltration in the peri-hematoma tissues were significantly reduced. Conclusions. Our observations suggest that microglia activation could be inhibited by HAESCs both in vitro and in vivo, which may be an important mechanism by which the transplantation of HAESCs reduces brain edema and ameliorates the neurologic deficits after ICH. Therefore, we hypothesize that methods for suppressing the activation of microglia and reducing the inflammatory response can be used for designing effective treatment strategies for ICH.