Comparing the angiogenic potency of naïve marrow stromal cells and Notch-transfected marrow stromal cells.
Comparing the angiogenic potency of naïve marrow stromal cells and Notch-transfected marrow stromal cells.
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DOI：
10.1186/1479-5876-11-81
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发表时间：
2013-03-27
影响因子：
7.4
通讯作者：
Case CC
中科院分区：
文献类型：
--
作者：
Dao M;Tate CC;McGrogan M;Case CC
血管生成是脑损伤和疾病中内源性修复过程的关键部分，并且需要至少两个连续步骤。首先，发生内皮细胞的血管生成发芽，这需要内皮细胞的初始增殖和周围细胞外基质的重塑。其次，血管稳定是防止血管退化所必需的，血管退化依赖于血管平滑肌募集来包围年轻血管。骨髓基质细胞（MSC）已被证明可以促进后肢缺血，心脏缺血和中风后的血管重建。SB 623细胞是通过用Notch1胞内结构域（NICD）表达质粒转染而从骨髓基质细胞衍生的，并且已知其在实验性中风中引起功能改善。这些细胞目前用于治疗慢性中风的人类临床试验。在目前的研究中，SB623细胞的血管生成特性进行了研究，使用基于细胞的测定。用Qantibody Human Angiogenesis Array鉴定SB623细胞和亲本MSCs分泌的血管生成旁分泌因子。为了测量来自SB 623细胞和MSC的条件培养基的血管生成活性，对人脐静脉内皮细胞（HUVEC）测定中的内皮管形成和啮齿动物主动脉环测定中的内皮细胞发芽和分支进行定量。为了验证VEGF在条件培养基中的血管生成贡献，用低剂量抑制VEGFR2的SU5416处理内皮细胞和主动脉环。SB623细胞的条件培养基在无血清条件下促进内皮细胞的存活和增殖，并支持HUVEC血管管的形成。在啮齿动物主动脉环试验中，SB623衍生的条件培养基增强了内皮发芽和分支。SU5416处理部分逆转了条件培养基对内皮细胞存活和增殖的影响，同时完全消除了主动脉环试验中的HUVEC管形成和内皮细胞出芽和分支。这些数据表明，SB623细胞分泌的血管生成因子促进了血管生成的几个方面，这可能有助于促进受损脑的恢复。
Angiogenesis is a critical part of the endogenous repair process in brain injury and disease, and requires at least two sequential steps. First, angiogenic sprouting of endothelial cells occurs, which entails the initial proliferation of endothelial cells and remodeling of the surrounding extracellular matrix. Second, vessel stabilization is necessary to prevent vascular regression, which relies on vascular smooth muscle recruitment to surround the young vessels. Marrow stromal cells (MSCs) have been shown to promote revascularization after hindlimb ischemia, cardiac ischemia, and stroke. SB623 cells are derived from marrow stromal cells by transfection with a Notch1 intracellular domain (NICD)-expressing plasmid and are known to elicit functional improvement in experimental stroke. These cells are currently used in human clinical testing for treatment of chronic stroke. In the current study, the angiogenic property of SB623 cells was investigated using cell-based assays. Angiogenic paracrine factors secreted by SB623 cells and the parental MSCs were identified using the Qantibody Human Angiogenesis Array. To measure the angiogenic activity of conditioned medium from SB623 cells and MSCs, endothelial tube formation in the human umbilical vein endothelial cell (HUVEC) assay and endothelial cell sprouting and branching in the rodent aortic ring assay were quantified. To validate the angiogenic contribution of VEGF in conditioned medium, endothelial cells and aortic rings were treated with SU5416, which inhibits VEGFR2 at low dose. Conditioned medium from SB623 cells promoted survival and proliferation of endothelial cells under serum-deprived conditions and supports HUVEC vascular tube formation. In a rodent aortic ring assay, there was enhanced endothelial sprouting and branching in response to SB623-derived conditioned medium. SU5416 treatment partially reversed the effect of conditioned medium on endothelial cell survival and proliferation while completely abrogate HUVEC tube formation and endothelial cell sprouting and branching in aortic ring assays. These data indicate that SB623 cell-secreted angiogenic factors promoted several aspects of angiogenesis, which likely contribute to promoting recovery in the injured brain.
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影响因子：
9.3
作者：
Dao MA;Tate CC;Aizman I;McGrogan M;Case CC
通讯作者：
Case CC
DOI：
10.3109/08977199109000278
发表时间：
1991-01-01
期刊：
Growth factors (Chur, Switzerland)
影响因子：
--
作者：
Ferrara, N;Winer, J;Burton, T
通讯作者：
Burton, T
影响因子：
20.1
作者：
YUE, TL;WANG, X;FEUERSTEIN, GZ
通讯作者：
FEUERSTEIN, GZ
影响因子：
2.9
作者：
Omori Y;Honmou O;Harada K;Suzuki J;Houkin K;Kocsis JD
通讯作者：
Kocsis JD
影响因子：
5.3
作者：
Ohab, John J.;Fleming, Sheila;Carmichael, S. Thomas
通讯作者：
Carmichael, S. Thomas