The modulation of cardiac progenitor cell function by hydrogel-dependent Notch1 activation.
The modulation of cardiac progenitor cell function by hydrogel-dependent Notch1 activation.
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DOI：
10.1016/j.biomaterials.2014.05.082
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发表时间：
2014-09
期刊：
影响因子：
14
通讯作者：
Davis, Michael E.
中科院分区：
文献类型：
--
作者：
Boopathy, Archana V.;Che, Pao Lin;Somasuntharam, Inthirai;Fiore, Vincent F.;Cabigas, E. Bernadette;Ban, Kiwon;Brown, Milton E.;Narui, Yoshie;Barker, Thomas H.;Yoon, Young-Sup;Salaita, Khalid;Garcia, Andres J.;Davis, Michael E.
心肌梗死是世界范围内死亡的主要原因，利用心脏祖细胞（CPC）的I期临床试验已显示出有希望的结果。Notch 1信号在心脏发育和心脏干/祖细胞的存活、心源性谱系定型和分化中起关键作用。在这项研究中，我们功能化的自组装肽（SAP）水凝胶与肽模拟的Notch 1配体锯齿状蛋白1（RJ），以评估在大鼠心肌梗死模型的水凝胶中的CPC输送的治疗效益。评价了在三维水凝胶中体外培养的CPC的行为，包括基因表达、增殖和生长因子产生。有趣的是，我们观察到Notch 1活化依赖于水凝胶聚合物密度/刚度，在RJ存在下协同增加。我们的研究结果表明，RJ介导的Notch 1激活依赖于水凝胶浓度差异调节心源性基因的表达，增殖和生长因子的生产在体外CPC。在经历实验性心肌梗死的大鼠中，与未修饰的或含有乱序肽的水凝胶相比，在RJ水凝胶中的细胞治疗后观察到急性滞留和心脏功能的改善。该研究证明了用RJ官能化SAP水凝胶用于基于CPC的心脏修复的潜在治疗益处。
Myocardial infarction is the leading cause of death worldwide and phase I clinical trials utilizing cardiac progenitor cells (CPCs) have shown promising outcomes. Notch1 signaling plays a critical role in cardiac development and in the survival, cardiogenic lineage commitment, and differentiation of cardiac stem/progenitor cells. In this study, we functionalized self-assembling peptide (SAP) hydrogels with a peptide mimic of the Notch1 ligand Jagged1 (RJ) to evaluate the therapeutic benefit of CPC delivery in the hydrogels in a rat model of myocardial infarction. The behavior of CPCs cultured in the 3D hydrogels in vitro including gene expression, proliferation, and growth factor production was evaluated. Interestingly, we observed Notch1 activation to be dependent on hydrogel polymer density/stiffness with synergistic increase in presence of RJ. Our results show that RJ mediated Notch1 activation depending on hydrogel concentration differentially regulated cardiogenic gene expression, proliferation, and growth factor production in CPCs in vitro. In rats subjected to experimental myocardial infarction, improvement in acute retention and cardiac function was observed following cell therapy in RJ hydrogels compared to unmodified or scrambled peptide containing hydrogels. This study demonstrates the potential therapeutic benefit of functionalizing SAP hydrogels with RJ for CPC based cardiac repair.
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影响因子：
37.8
作者：
Go AS;Mozaffarian D;Roger VL;Benjamin EJ;Berry JD;Blaha MJ;Dai S;Ford ES;Fox CS;Franco S;Fullerton HJ;Gillespie C;Hailpern SM;Heit JA;Howard VJ;Huffman MD;Judd SE;Kissela BM;Kittner SJ;Lackland DT;Lichtman JH;Lisabeth LD;Mackey RH;Magid DJ;Marcus GM;Marelli A;Matchar DB;McGuire DK;Mohler ER 3rd;Moy CS;Mussolino ME;Neumar RW;Nichol G;Pandey DK;Paynter NP;Reeves MJ;Sorlie PD;Stein J;Towfighi A;Turan TN;Virani SS;Wong ND;Woo D;Turner MB;American Heart Association Statistics Committee and Stroke Statistics Subcommittee
通讯作者：
American Heart Association Statistics Committee and Stroke Statistics Subcommittee
影响因子：
14
作者：
Liu, Jie;Gu, Catherine;Cabigas, E. Bernadette;Pendergrass, Karl D.;Brown, Milton E.;Luo, Ying;Davis, Michael E.
通讯作者：
Davis, Michael E.
影响因子：
24
作者：
Ellison, Georgina M.;Torella, Daniele;Nadal-Ginard, Bernardo
通讯作者：
Nadal-Ginard, Bernardo
影响因子：
9.5
作者：
Kuang, Dong;Zhao, Xia;Wang, Guoping
通讯作者：
Wang, Guoping
影响因子：
10.8
作者：
Gelain, Fabrizio;Unsworth, Larry D.;Zhang, Shuguang
通讯作者：
Zhang, Shuguang