Capturing the stem cell paracrine effect using heparin-presenting nanofibres to treat cardiovascular diseases.
Capturing the stem cell paracrine effect using heparin-presenting nanofibres to treat cardiovascular diseases.
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DOI：
10.1002/term.273
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发表时间：
2010-12
影响因子：
3.3
通讯作者：
Lomasney JW
中科院分区：
文献类型：
--
作者：
Webber MJ;Han X;Murthy SN;Rajangam K;Stupp SI;Lomasney JW
干细胞介导的急性心肌梗死后改善的机制一直备受争议。我们支持干细胞效应主要与旁分泌因子相关的假设。我们使用肝素呈递的可注射纳米纤维网络来结合和传递来自低氧条件干细胞培养液的旁分泌因子，以模拟这种干细胞旁分泌效应。我们的呈现肝素的自组装多肽纳米纤维能够结合介质相中的旁分泌因子。在急性心肌梗死的小鼠缺血-再灌注模型中，当在冠状动脉结扎后将这些因子负载材料注入心脏时，我们发现显著地保存了血流动力学功能。通过媒体操纵，我们能够确定关键因素主要是小于30 kDa的，主要是肝素结合。利用重组血管内皮生长因子和碱性成纤维细胞生长因子负载纳米纤维网络，对条件培养液的作用进行了总结。当在另一种疾病模型--慢性大鼠缺血后肢中进行评估时，我们的因子负载材料有助于广泛的肢体血运重建。这些实验证明了与干细胞治疗相关的旁分泌效应的效力，以及生物材料结合和传递这些因子的潜力，指出了一种基于合成材料和重组因子的潜在疗法作为一种无细胞疗法。
The mechanism for stem cell mediated improvement following acute myocardial infarction has been actively debated. We support hypotheses that the stem cell effect is primarily paracrine factor-linked. We used a heparin-presenting injectable nanofiber network to bind and deliver paracrine factors derived from hypoxic conditioned stem cell media to mimic this stem cell paracrine effect. Our self-assembling peptide nanofibers presenting heparin were capable of binding paracrine factors from a media phase. When these factor-loaded materials were injected into the heart following coronary artery ligation in a mouse ischemia-reperfusion model of acute myocardial infarction, we found significant preservation of hemodynamic function. Through media manipulation, we were able to determine that crucial factors are primarily less than 30 kDa and primarily heparin-binding. Using recombinant VEGF and bFGF loaded nanofiber networks the effect observed with conditioned media was recapitulated. When evaluated in another disease model, a chronic rat ischemic hind limb, our factor-loaded materials contributed to extensive limb revascularization. These experiments demonstrate the potency of the paracrine effect associated with stem cell therapies and the potential of a biomaterial to bind and deliver these factors, pointing to a potential therapy based on synthetic materials and recombinant factors as an acellular therapy.
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影响因子：
14
作者：
Ghanaati, Shahram;Webber, Matthew J.;Unger, Ronald E.;Orth, Carina;Hulvat, James F.;Kiehna, Sarah E.;Barbeck, Mike;Rasic, Angela;Stupp, Samuel I.;Kirkpatrick, C. James
通讯作者：
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通讯作者：
Itescu, S
影响因子：
39.3
作者：
Freyman, T;Polin, G;Wilensky, RL
通讯作者：
Wilensky, RL