Cell Injury-Induced Release of Fibroblast Growth Factor 2: Relevance to Intracerebral Mesenchymal Stromal Cell Transplantations.
Cell Injury-Induced Release of Fibroblast Growth Factor 2: Relevance to Intracerebral Mesenchymal Stromal Cell Transplantations.
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DOI：
10.1089/scd.2015.0083
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发表时间：
2015-07-15
影响因子：
4
通讯作者：
Bates D
中科院分区：
文献类型：
--
作者：
Aizman I;Vinodkumar D;McGrogan M;Bates D
间充质基质细胞（MSC）及其衍生物脑内移植的有益效果被认为主要是由植入细胞产生的因子介导的。然而，间充质细胞植入率低，并且大多数移植细胞在移植后短时间内消失。在这里，我们假设垂死的移植细胞可以通过释放它们的活性细胞内成分来影响周围组织。为了阐明这些推定的细胞内因子的类型、数量和效力，在酶联免疫吸附测定和生物测定中测试MSC或其衍生物的冻融提取物。我们发现，成纤维细胞生长因子（FGF）2和FGF1，但不是血管内皮生长因子和单核细胞趋化蛋白1的水平是高的提取物，尽管在条件培养基低。提取物诱导大鼠皮质神经祖细胞和人脐静脉内皮细胞的浓度依赖性增殖，这些增殖反应被特异性阻断FGF2中和抗体。在大鼠皮质细胞的神经生成试验中，MSC提取物和杀死的细胞都诱导巢蛋白的表达，但不诱导星形胶质细胞分化。然而，杀死的细胞的悬浮液强烈地增强了活MSC的星形作用。在移植相关MSC损伤模型（外周血细胞介导的细胞毒性和高细胞密度铺板）中，MSC死亡与细胞内FGF 2的释放一致。数据显示，MSC含有活性FGF 2的主要储存库，其在细胞损伤时释放，并且能够急性刺激神经生成和血管生成。因此，我们认为死亡和存活的移植MSC都有助于组织再生。
Beneficial effects of intracerebral transplantation of mesenchymal stromal cells (MSC) and their derivatives are believed to be mediated mostly by factors produced by engrafted cells. However, the mesenchymal cell engraftment rate is low, and the majority of grafted cells disappear within a short post-transplantation period. Here, we hypothesize that dying transplanted cells can affect surrounding tissues by releasing their active intracellular components. To elucidate the type, amounts, and potency of these putative intracellular factors, freeze/thaw extracts of MSC or their derivatives were tested in enzyme-linked immunosorbent assays and bioassays. We found that fibroblast growth factor (FGF)2 and FGF1, but not vascular endothelial growth factor and monocyte chemoattractant protein 1 levels were high in extracts despite being low in conditioned media. Extracts induced concentration-dependent proliferation of rat cortical neural progenitor cells and human umbilical vein endothelial cells; these proliferative responses were specifically blocked by FGF2-neutralizing antibody. In the neuropoiesis assay with rat cortical cells, both MSC extracts and killed cells induced expression of nestin, but not astrocyte differentiation. However, suspensions of killed cells strongly potentiated the astrogenic effects of live MSC. In transplantation-relevant MSC injury models (peripheral blood cell-mediated cytotoxicity and high cell density plating), MSC death coincided with the release of intracellular FGF2. The data showed that MSC contain a major depot of active FGF2 that is released upon cell injury and is capable of acutely stimulating neuropoiesis and angiogenesis. We therefore propose that both dying and surviving grafted MSC contribute to tissue regeneration.
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影响因子：
5.6
作者：
GAJDUSEK, CM;CARBON, S
通讯作者：
CARBON, S
影响因子：
6
作者：
Aizman, Irina;McGrogan, Michael;Case, Casey C.
通讯作者：
Case, Casey C.
影响因子：
20.1
作者：
Cheng, GC;Briggs, WH;Lee, RT
通讯作者：
Lee, RT
影响因子：
11.2
作者：
Bang, OY;Lee, JS;Lee, G
通讯作者：
Lee, G
影响因子：
7.4
作者：
Dao M;Tate CC;McGrogan M;Case CC
通讯作者：
Case CC