A novel platelet lysate hydrogel for endothelial cell and mesenchymal stem cell-directed neovascularization.
A novel platelet lysate hydrogel for endothelial cell and mesenchymal stem cell-directed neovascularization.
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DOI：
10.1016/j.actbio.2016.03.002
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发表时间：
2016-05
影响因子：
9.7
通讯作者：
Brewster LP
中科院分区：
文献类型：
--
作者：
Robinson ST;Douglas AM;Chadid T;Kuo K;Rajabalan A;Li H;Copland IB;Barker TH;Galipeau J;Brewster LP
间充质干细胞（MSC）有望在腿部严重肢体缺血等情况下促进缺血组织的血管再生。然而，这种方法在一定程度上受到细胞保留和交付后存活率差的限制。新的生物材料提供了在递送后将细胞定位到所需组织的机会，而且还提供了在递送后提高细胞存活率的机会。在这里，我们表征了一种新的水凝胶的机械和微观结构特性组成的汇集人血小板裂解物（PL）和测试其能力，以促进MSC血管生成活性，使用临床相关的体外和体内模型。该PL水凝胶具有相当的储能模量和损耗模量，并且表现为类似于纤维蛋白水凝胶的粘弹性固体，尽管具有标准纤维蛋白凝胶的1/4-1/10的纤维蛋白含量。此外，PL水凝胶能够持续释放内源性PDGF-BB长达20天，并且对蛋白酶降解具有抗性。PL水凝胶通过促进人MSC在3D环境中的生长和侵袭，以及单独和与MSC共培养时增强内皮细胞发芽来刺激促血管生成活性。当在体内递送时，与对照相比，PL和人MSC的组合在后肢缺血的鼠模型中用激光多普勒灌注成像评估时在8天后改善了局部组织灌注。这些结果支持使用PL水凝胶作为MSC递送的支架以促进血管再生。
Mesenchymal stem cells (MSC) hold promise in promoting vascular regeneration of ischemic tissue in conditions like critical limb ischemia of the leg. However, this approach has been limited in part by poor cell retention and survival after delivery. New biomaterials offer an opportunity to localize cells to the desired tissue after delivery, but also to improve cell survival after delivery. Here we characterize the mechanical and microstructural properties of a novel hydrogel composed of pooled human platelet lysate (PL) and test its ability to promote MSC angiogenic activity using clinically relevant in vitro and in vivo models. This PL hydrogel had comparable storage and loss modulus and behaved as a viscoelastic solid similar to fibrin hydrogels despite having 1/4-1/10th the fibrin content of standard fibrin gels. Additionally, PL hydrogels enabled sustained release of endogenous PDGF-BB for up to 20 days and were resistant to protease degradation. PL hydrogel stimulated pro-angiogenic activity by promoting human MSC growth and invasion in a 3D environment, and enhancing endothelial cell sprouting alone and in co-culture with MSCs. When delivered in vivo, the combination of PL and human MSCs improved local tissue perfusion after 8 days compared to controls when assessed with laser Doppler perfusion imaging in a murine model of hind limb ischemia. These results support the use of a PL hydrogel as a scaffold for MSC delivery to promote vascular regeneration.