利用生長(zhǎng)因子催生新血管的研究,，一直面臨如何讓生長(zhǎng)因子穩(wěn)定存在并與血管細(xì)胞結(jié)合等問題,。美國(guó)科研人員通過動(dòng)物實(shí)驗(yàn),，利用兩種物質(zhì)促進(jìn)上述問題的解決，生成了類似小動(dòng)脈的血管,。
來自匹茲堡大學(xué)的研究者在新一期美國(guó)《國(guó)家科學(xué)院院刊》（PNAS）上報(bào)告說,，人和一些動(dòng)物體內(nèi)都存在控制細(xì)胞增殖、移動(dòng)和分化的生長(zhǎng)因子,，由于它們的這些功能很強(qiáng)大,，機(jī)體會(huì)嚴(yán)格控制這類生長(zhǎng)因子，因醫(yī)學(xué)研究而注入機(jī)體,、可以移動(dòng)的生長(zhǎng)因子會(huì)很快被機(jī)體消滅,。
為解決這一難題，匹茲堡大學(xué)的研究者篩選出一種肝磷脂分子,，它能一手牽著生長(zhǎng)因子,，一手拉住血管細(xì)胞的表面受體，從而使生長(zhǎng)因子在血管細(xì)胞上穩(wěn)定生存一段時(shí)間,。
但新的問題隨之而來——肝磷脂與生長(zhǎng)因子結(jié)合而成的物質(zhì)是水溶性的,，在機(jī)體內(nèi)這種水溶性化合物在幾秒內(nèi)就會(huì)分解。為遲滯這種分解,，研究小組用一種聚陽離子對(duì)肝磷脂攜帶的負(fù)電荷進(jìn)行中和,，使肝磷脂與生長(zhǎng)因子的結(jié)合物由溶液轉(zhuǎn)化為像微小油滴一樣的凝聚層，從而為生長(zhǎng)因子催生血管贏得了時(shí)間,。
在實(shí)驗(yàn)中,，研究者將成纖維細(xì)胞生長(zhǎng)因子-2注入老鼠體內(nèi)，并運(yùn)用上述新方法使其在血管細(xì)胞表面穩(wěn)定下來，最終催生出新的大血管,，其結(jié)構(gòu)與小動(dòng)脈類似,，而小動(dòng)脈可以通往毛細(xì)血管網(wǎng)絡(luò)。該研究還顯示,，在僅注射一針生長(zhǎng)因子的條件下,，催生出的新血管可存活一個(gè)月有余。（生物谷 Bioon.com）
doi:10.1073/pnas.1110121108
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PMID:
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.
