Modulation of inflammatory responses after global ischemia by transplanted umbilical cord matrix stem cells.
Modulation of inflammatory responses after global ischemia by transplanted umbilical cord matrix stem cells.
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DOI：
10.1634/stemcells.2008-0075
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发表时间：
2008-11
期刊：
影响因子：
--
通讯作者：
Xu Y
中科院分区：
文献类型：
--
作者：
Hirko AC;Dallasen R;Jomura S;Xu Y
大鼠脐带基质（RUCM）细胞是干细胞样细胞，已被证明可以减少心脏骤停（CA）后选择性脆弱大脑区域的神经元丢失。在这里，我们研究这种保护是否是由RUCM细胞对缺血后炎症反应的调节介导的，缺血后炎症反应长期以来一直被认为是缺血后损伤的次要机制。用化学方法检查脑切片的GFAP、波形蛋白和巢蛋白作为星形胶质细胞和反应性星形胶质细胞增生的标志物，蓖麻凝集素-1（RCA-1）作为小胶质细胞的标志物，Ki 67作为细胞增殖的标志物。将大鼠随机分为6个实验组：（1）8 min CA未处理，（2）8 min CA预处理培养基注射，（3）8 min CA预处理RUCM细胞，（4）假手术CA，（5）培养基注射无CA，（6）RUCM细胞移植无CA。与组4-6相比，组1-3在海马CA 1区具有显著更高的Ki 67+细胞计数和更高的GFAP+免疫反应性，无论处理如何。组1和组2具有高度升高的GFAP+、波形蛋白+和巢蛋白+免疫反应性，表明反应性星形胶质细胞增生。引人注目的是，RUCM细胞处理几乎完全抑制波形蛋白+的出现，并大大减少巢蛋白+反应性星形胶质细胞。RUCM细胞处理也大大降低了RCA-1的表达，这被发现与CA 1区域的神经元损失密切相关。我们的研究表明，干细胞样RUCM细胞治疗调节炎症反应，全球缺血，并通过防止永久性损伤的选择性脆弱的星形胶质细胞在CA 1区提供神经元保护。
Rat umbilical cord matrix (RUCM) cells are stem-cell-like cells and have been shown to reduce neuronal loss in the selectively vulnerable brain regions after cardiac arrest (CA). Here, we investigate whether this protection is mediated by the RUCM cells’ modulation of the post-ischemia inflammation responses, which have long been implicated as a secondary mechanism of injury following ischemia. Brain sections were examined immunohistochemically for GFAP, vimentin, and nestin as markers for astroglia and reactive astrogliosis, Ricinus Communis Agglutinin-1 (RCA-1) as a marker for microglia, and Ki67 as a marker for cell proliferation. Rats were randomly assigned to six experimental groups: (1) 8-min CA without treatment, (2) 8-min CA pretreated with culture medium injection, (3) 8-min CA pretreated with RUCM cells, (4) sham-operated CA, (5) medium injection without CA, and (6) RUCM cell transplantation without CA. Groups 1–3 have significantly higher Ki67+ cell counts and higher GFAP+ immunoreactivity in the hippocampal CA1 region compared to groups 4–6, irrespective of treatment. Groups 1 and 2 have highly elevated GFAP+, vimentin+, and nestin+ immunoreactivity, indicating reactive astrogliosis. Strikingly, RUCM cell treatment nearly completely inhibited the appearance of vimentin+ and greatly reduced nestin+ reactive astrocytes. RUCM cell treatment also greatly reduced RCA-1 expression, which is found to strongly correlate with the neuronal loss in the CA1 region. Our study indicates that treatment with stem-cell-like RUCM cells modulates the inflammatory response to global ischemia and renders neuronal protection by preventing permanent damage to the selectively vulnerable astrocytes in the CA1 region.
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