PNAS：匹兹堡大学用强力生长因子催生新血管
利用生长因子催生新血管的研究，一直面临如何让生长因子稳定存在并与血管细胞结合等问题。美国科研人员通过动物实验，利用两种物质促进上述问题的解决，生成了类似小动脉的血管。
来自匹兹堡大学的研究者在新一期美国《国家科学院院刊》（PNAS）上报告说，人和一些动物体内都存在控制细胞增殖、移动和分化的生长因子，由于它们的这些功能很强大，机体会严格控制这类生长因子，因医学研究而注入机体、可以移动的生长因子会很快被机体消灭。
为解决这一难题，匹兹堡大学的研究者筛选出一种肝磷脂分子，它能一手牵着生长因子，一手拉住血管细胞的表面受体，从而使生长因子在血管细胞上稳定生存一段时间。
但新的问题随之而来——肝磷脂与生长因子结合而成的物质是水溶性的，在机体内这种水溶性化合物在几秒内就会分解。为迟滞这种分解，研究小组用一种聚阳离子对肝磷脂携带的负电荷进行中和，使肝磷脂与生长因子的结合物由溶液转化为像微小油滴一样的凝聚层，从而为生长因子催生血管赢得了时间。
在实验中，研究者将成纤维细胞生长因子-2注入老鼠体内，并运用上述新方法使其在血管细胞表面稳定下来，最终催生出新的大血管，其结构与小动脉类似，而小动脉可以通往毛细血管网络。该研究还显示，在仅注射一针生长因子的条件下，催生出的新血管可存活一个月有余
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Injectable fibroblast growth factor-2 coacervate for persistent angiogenesis
Chu, Hunghao; Gao, Jin; Chen, Chien-Wen; Huard, Johnny; Wang, Yadong
Enhancing the maturity of the newly formed blood vessels is critical for the success of therapeutic angiogenesis. The maturationof vasculature relies on active participation of mural cells to stabilize endothelium and a basal level of relevant growthfactors. We set out to design and successfully achieved robust angiogenesis using an injectable polyvalent coacervate of apolycation, heparin, and fibroblast growth factor-2 (FGF2). FGF2 was loaded into the coacervate at nearly 100% efficiency.In vitro assays demonstrated that the matrix protected FGF2 from proteolytic degradations. FGF2 released from the coacervatewas more effective in the differentiation of endothelial cells and chemotaxis of pericytes than free FGF2. One injection of500 ng of FGF2 in the coacervate elicited comprehensive angiogenesis in vivo. The number of endothelial and mural cells increasedsignificantly, and the local tissue contained more and larger blood vessels with increased circulation. Mural cells activelyparticipated during the whole angiogenic process: Within 7 d of the injection, pericytes were recruited to close proximityof the endothelial cells. Mature vasculature stabilized by vascular smooth muscle cells persisted till at least 4 wk. On theother hand, bolus injection of an identical amount of free FGF2 induced weak angiogenic responses. These results demonstratethe potential of polyvalent coacervate as a new controlled delivery platform.
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