Pharmacologically active microcarriers influence VEGF-A effects on mesenchymal stem cell survival.
Pharmacologically active microcarriers influence VEGF-A effects on mesenchymal stem cell survival.
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DOI：
10.1111/j.1582-4934.2012.01662.x
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发表时间：
2013-01
影响因子：
5.3
通讯作者：
Pagliaro P
中科院分区：
文献类型：
--
作者：
Penna C;Perrelli MG;Karam JP;Angotti C;Muscari C;Montero-Menei CN;Pagliaro P
缺血后心脏中移植的间充质干细胞（MSC）的抵抗力因其较差的活力而受到限制。血管内皮生长因子-A (VEGF-A) 本身或由纤连蛋白包被的药理活性微载体 (FN-PAM-VEGF) 缓慢释放可能会不同地影响存活激酶和抗凋亡介质（例如 Bcl-2）。因此，VEGF-A或FN-PAM-VEGF可以不同地增强MSC的细胞增殖和/或对缺氧/复氧（H/R）的抵抗力。为了测试这些假设，将 MSC 与单独的 VEGF-A 或与 FN-PAM-VEGF 一起孵育 6 天。此外，用 VEGF-A 或 FN-PAM-VEGF 预处理 24 小时的 MSC 随后暴露于 H/R（72 小时 3% O2 和 3 小时复氧）。测定细胞增殖和缺氧后活力。在治疗 30 分钟、1 天和 3 天时对激酶进行研究。 VEGF-A 治疗后 6 天，细胞增殖增加约两倍 (P < 0.01)，但 FN-PAM-VEGF 治疗后，细胞增殖程度较小 (增加 55%) (P < 0.05)。虽然用 VEGF-A 预处理 MSC 证实了细胞增殖，但用 FN-PAM-VEGF 预处理可保护 MSC 免受 H/R 的影响。在治疗的早期阶段，与未处理的细胞或 FN-PAM-VEGF 相比，VEGF-A 增加了磷酸-Akt、磷酸-ERK-1/2 和磷酸-PKCε。后记，VGEF 组的激酶磷酸化水平更高，但 ERK-1/2 除外，这两种治疗在第 3 天时的激酶磷酸化水平类似。仅 FN-PAM-VEGF 显着增加 Bcl-2 水平。 H/R 后，乳酸脱氢酶释放和裂解的 Caspase-3 水平主要由 FN-PAM-VEGF 降低。虽然 VEGF-A 在常氧条件下增强 MSC 增殖，但 FN-PAM-VEGF 主要阻碍缺氧后 MSC 死亡。这些不同的影响强调了适合不同条件的方法的必要性。 FN-PAM-VEGF的使用可被认为是增强MSC在缺血后组织的恶劣环境中存活和再生的新方法。
Resistance of transplanted mesenchymal stem cells (MSCs) in post-ischemic heart is limited by their poor vitality. Vascular-endothelial-growth-factor-A (VEGF-A) as such or slowly released by fibronectin-coated pharmacologically-active-microcarriers (FN-PAM-VEGF) could differently affect survival kinases and anti-apoptotic mediator (e.g. Bcl-2). Therefore VEGF-A or FN-PAM-VEGF could differently enhance cell proliferation, and/or resistance to hypoxia/reoxygenation (H/R) of MSCs. To test these hypotheses MSCs were incubated for 6-days with VEGF-A alone or with FN-PAM-VEGF. In addition, MSCs pre-treated for 24-hrs with VEGF-A or FN-PAM-VEGF were subsequently exposed to H/R (72-hrs 3% O2 and 3-hrs of reoxygenation). Cell-proliferation and post-hypoxic vitality were determined. Kinases were studied at 30-min., 1- and 3-days of treatment. Cell-proliferation increased about twofold (P < 0.01) 6-days after VEGF-A treatment, but by a lesser extent (55% increase) with FN-PAM-VEGF (P < 0.05). While MSC pre-treatment with VEGF-A confirmed cell-proliferation, pre-treatment with FN-PAM-VEGF protected MSCs against H/R. In the early phase of treatments, VEGF-A increased phospho-Akt, phospho-ERK-1/2 and phospho-PKCε compared to the untreated cells or FN-PAM-VEGF. Afterword, kinase phosphorylations were higher with VGEF, except for ERK-1/2, which was similarly increased by both treatments at 3 days. Only FN-PAM-VEGF significantly increased Bcl-2 levels. After H/R, lactate dehydrogenase release and cleaved Caspase-3 levels were mainly reduced by FN-PAM-VEGF. While VEGF-A enhances MSC proliferation in normoxia, FN-PAM-VEGF mainly hampers post-hypoxic MSC death. These different effects underscore the necessity of approaches suited to the various conditions. The use of FN-PAM-VEGF could be considered as a novel approach for enhancing MSC survival and regeneration in hostile environment of post-ischemic tissues.
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血管内皮生长因子可以通过血小板衍生的生长因子受体发出信号。
影响因子：
7.8
作者：
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通讯作者：
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发表时间：
2008-09-01
影响因子：
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作者：
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