The role of macrophage phenotype in vascularization of tissue engineering scaffolds.
The role of macrophage phenotype in vascularization of tissue engineering scaffolds.
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DOI：
10.1016/j.biomaterials.2014.02.012
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发表时间：
2014-05
期刊：
影响因子：
14
通讯作者：
Vunjak-Noyakovic, Gordana
中科院分区：
文献类型：
--
作者：
Spiller, Kara L.;Anfang, Rachel R.;Spiller, Krista J.;Ng, Johnathan;Nakazawa, Kenneth R.;Daulton, Jeffrey W.;Vunjak-Noyakovic, Gordana
血管生成对于大多数组织工程策略的成功至关重要。天然炎症反应是血管形成的主要调节因子，通过不同类型的巨噬细胞及其分泌的细胞因子的活性。巨噬细胞存在于一系列不同的表型上，从“经典活化”的M1到“替代活化”的M2巨噬细胞。M2巨噬细胞，包括亚群M2 a和M2 c，通常被认为是促进血管生成和组织再生，而M1巨噬细胞被认为是抗血管生成的，尽管这些分类是有争议的。在这里，我们表明，在这种传统的范例相反，原代人M1巨噬细胞分泌最高水平的有效的血管生成刺激因子，包括VEGF; M2 a巨噬细胞分泌最高水平的PDGF-BB，一种化学引诱剂稳定周细胞，也促进吻合的萌芽内皮细胞在体外;和M2 c巨噬细胞分泌最高水平的MMP 9，一种重要的蛋白酶参与血管重塑。在小鼠皮下植入模型中，多孔胶原支架被纤维囊包围，与M2巨噬细胞标志物的高表达一致，而涂覆有细菌脂多糖的支架被炎性巨噬细胞降解，并且戊二醛交联的支架被大量血管浸润，伴随着高水平的M1和M2巨噬细胞。这些结果表明，M1和M2巨噬细胞的协调努力是血管生成和支架血管化所必需的，这可以解释哪些表型是血管生成表型的一些争议。
Angiogenesis is crucial for the success of most tissue engineering strategies. The natural inflammatory response is a major regulator of vascularization, through the activity of different types of macrophages and the cytokines they secrete. Macrophages exist on a spectrum of diverse phenotypes, from “classically activated” M1 to “alternatively activated” M2 macrophages. M2 macrophages, including the subsets M2a and M2c, are typically considered to promote angiogenesis and tissue regeneration, while M1 macrophages are considered to be anti-angiogenic, although these classifications are controversial. Here we show that in contrast to this traditional paradigm, primary human M1 macrophages secrete the highest levels of potent angiogenic stimulators including VEGF; M2a macrophages secrete the highest levels of PDGF-BB, a chemoattractant stabilizing pericytes, and also promote anastomosis of sprouting endothelial cells in vitro; and M2c macrophages secrete the highest levels of MMP9, an important protease involved in vascular remodeling. In a murine subcutaneous implantation model, porous collagen scaffolds were surrounded by a fibrous capsule, coincident with high expression of M2 macrophage markers, while scaffolds coated with the bacterial lipopolysaccharide were degraded by inflammatory macrophages, and glutaraldehyde-crosslinked scaffolds were infiltrated by substantial numbers of blood vessels accompanied by high levels of M1 and M2 macrophages. These results suggest that coordinated efforts by both M1 and M2 macrophages are required for angiogenesis and scaffold vascularization, which may explain some of the controversy over which phenotype is the angiogenic phenotype.
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DOI：
10.1073/pnas.1300290110
发表时间：
2013-06-04
影响因子：
11.1
作者：
Godwin, James W.;Pinto, Alexander R.;Rosenthal, Nadia A.
通讯作者：
Rosenthal, Nadia A.
DOI：
10.1038/nrm3176
发表时间：
2011-08-23
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1007/978-3-540-78281-0_7
发表时间：
2010-01-01
期刊：
ANGIOGENESIS INHIBITION
影响因子：
--
作者：
Hellberg, Carina;Ostman, Arne;Heldin, C. -H.
通讯作者：
Heldin, C. -H.
影响因子：
20.3
作者：
Fantin, Alessandro;Vieira, Joaquim M.;Ruhrberg, Christiana
通讯作者：
Ruhrberg, Christiana
DOI：
10.1161/atvbaha.113.301164
发表时间：
2013-05
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Eirin A;Zhu XY;Li Z;Ebrahimi B;Zhang X;Tang H;Korsmo MJ;Chade AR;Grande JP;Ward CJ;Simari RD;Lerman A;Textor SC;Lerman LO
通讯作者：
Lerman LO