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首页> 外文期刊>Acta biomaterialia >Development of bioactive peptide amphiphiles for therapeutic cell delivery.
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Development of bioactive peptide amphiphiles for therapeutic cell delivery.

机译：生物活性肽两亲递送生物活性肽两亲。

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There is great clinical interest in cell-based therapies for ischemic tissue repair in cardiovascular disease. However, the regenerative potential of these therapies is limited due to poor cell viability and minimal retention following application. We report here the development of bioactive peptide amphiphile nanofibers displaying the fibronectin-derived RGDS cell adhesion epitope as a scaffold for therapeutic delivery of bone marrow derived stem and progenitor cells. When grown on flat substrates, a binary peptide amphiphile system consisting of 10 wt.% RGDS-containing molecules and 90wt.% negatively charged diluent molecules was found to promote optimal cell adhesion. This binary system enhanced adhesion 1.4-fold relative to substrates composed of only the non-bioactive diluent. Additionally, no enhancement was found upon scrambling the epitope and adhesion was no longer enhanced upon adding soluble RGDS to the cell media, indicating RGDS-specific adhesion. When encapsulated within self-assembled scaffolds of the binary RGDS nanofibers in vitro, cells were found to be viable and proliferative, increasing in number by 5.5 times after only 5 days, an effect again lost upon adding soluble RGDS. Cells encapsulated within a non-bioactive scaffold and those within a binary scaffold with scrambled epitope showed minimal viability and no proliferation. Cells encapsulated within this RGDS nanofiber gel also increase in endothelial character, evident by a decrease in the expression of CD34 paired with an increase in the expression of endothelial-specific markers VE-Cadherin, VEGFR2 and eNOS after 5 days. In an in vivo study, nanofibers and luciferase-expressing cells were co-injected subcutaneously in a mouse model. The binary RGDS material supported these cells in vivo, evident by a 3.2-fold increase in bioluminescent signal attributable to viable cells; this suggests the material has an anti-apoptotic and/or proliferative effect on the transplanted bone marrow cells. We conclude that the binary RGDS-presenting nanofibers developed here demonstrate enhanced viability, proliferation and adhesion of associated bone marrow derived stem and progenitor cells. This study suggests potential for this material as a scaffold to overcome current limitations of stem cell therapies for ischemic diseases.
机译：心血管疾病缺血组织修复的基于细胞的疗法存在巨大的临床兴趣。然而，由于细胞活力差和施用之后的最小保留，这些疗法的再生潜力受到限制。我们在此报道了生物活性肽两亲纳米纤维的发展，其显示纤连蛋白衍生的RGDS细胞粘附表位作为骨髓衍生茎和祖细胞的治疗递送的支架。在平板上生长时，由10wt％的二元肽两亲物系统组成，包含含10重量％的分子和90wt.％带负电荷的稀释剂分子以促进最佳的细胞粘附。该二元系统相对于仅由非生物活性稀释剂组成的基材增强了1.4倍的粘附力。另外，在加扰表位时没有发现增强，并在将可溶性RGDS加入细胞介质时不再增强粘合，表明RGDS特异性粘附。当体外封装在二元RGDS纳米纤维的自组装支架内时，发现细胞是可行的和增殖的，仅在5天后增加5.5倍，在添加可溶性RGD时再次丧失。封装在非生物活性支架内的细胞和具有加扰表位的二元支架内的细胞显示出最小的存活率和不增殖。在该RGDS纳米纤维凝胶内包封的细胞也增加了内皮特征，通过CD34表达的降低，CD34的表达与5天后内皮特异性标记Ve-Cadherin的表达的增加，VEGFR2和ENOS的表达增加。在体内研究中，在小鼠模型中皮下共注射纳辉纤维和荧光素酶的细胞。二元RGDS材料在体内支持这些细胞，其具有可归解细胞的生物发光信号增加3.2倍;这表明该材料对移植的骨髓细胞具有抗凋亡和/或增殖作用。我们得出结论，在此开发的二元RGDS呈纳米纤维显示出相关的骨髓衍生的茎和祖细胞的增强的存活率，增殖和粘附性。本研究表明这种材料作为脚手架的潜力克服了干细胞疗法对缺血性疾病的电流限制。

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