IGF1 and NRG1 Enhance Proliferation, Metabolic Maturity, and the Force-Frequency Response in hESC-Derived Engineered Cardiac Tissues.
IGF1 and NRG1 Enhance Proliferation, Metabolic Maturity, and the Force-Frequency Response in hESC-Derived Engineered Cardiac Tissues.
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DOI：
10.1155/2017/7648409
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发表时间：
2017
影响因子：
4.3
通讯作者：
Coulombe KLK
中科院分区：
文献类型：
--
作者：
Rupert CE;Coulombe KLK
胰岛素样生长因子1（IGF 1）和神经调节蛋白1β（NRG 1）在心脏发育过程中发挥重要作用。在这项研究中，我们分析了如何从人胚胎干细胞（hESC）衍生的心肌细胞和2D平板hESC-心肌细胞工程化的三维心脏组织响应发育相关的生长因子，既刺激成熟，并表征IGF 1和NRG 1的治疗潜力。当给予工程化心脏组织时，在所有治疗组中测量到主动力产生显著降低约65%，这可能是由于细胞生理学的变化。在工程组织中鉴定了发育相关过程，因为IGF 1使hESC-心肌细胞增殖比未处理的对照增加3倍，并且NRG 1刺激氧化磷酸化，并在高达3 Hz的组织中促进正力-频率关系。在2D培养中，NRG 1和IGF 1 + NRG 1处理的hESC-心肌细胞面积显著增加，基因表达数据表明工程化组织中心脏收缩组分增加，表明需要在3D平台中进行功能分析以准确表征工程化心脏组织对生化刺激的反应。这项研究证明了IGF 1促进增殖和NRG 1促进工程化人类心脏组织代谢和收缩成熟的治疗潜力。
Insulin-like growth factor 1 (IGF1) and neuregulin-1β (NRG1) play important roles during cardiac development both individually and synergistically. In this study, we analyze how 3D cardiac tissue engineered from human embryonic stem cell- (hESC-) derived cardiomyocytes and 2D-plated hESC-cardiomyocytes respond to developmentally relevant growth factors both to stimulate maturity and to characterize the therapeutic potential of IGF1 and NRG1. When administered to engineered cardiac tissues, a significant decrease in active force production of ~65% was measured in all treatment groups, likely due to changes in cellular physiology. Developmentally related processes were identified in engineered tissues as IGF1 increased hESC-cardiomyocyte proliferation 3-fold over untreated controls and NRG1 stimulated oxidative phosphorylation and promoted a positive force-frequency relationship in tissues up to 3 Hz. hESC-cardiomyocyte area increased significantly with NRG1 and IGF1 + NRG1 treatment in 2D culture and gene expression data suggested increased cardiac contractile components in engineered tissues, indicating the need for functional analysis in a 3D platform to accurately characterize engineered cardiac tissue response to biochemical stimulation. This study demonstrates the therapeutic potential of IGF1 for boosting proliferation and NRG1 for promoting metabolic and contractile maturation in engineered human cardiac tissue.
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影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
3
作者：
Bielawski, Kevin S.;Leonard, Andrea;Sniadecki, Nathan J.
通讯作者：
Sniadecki, Nathan J.
影响因子：
7.7
作者：
Canto, Carles;Pich, Sara;Guma, Anna
通讯作者：
Guma, Anna
影响因子：
4.1
作者：
Hakkinen, Kirsi M.;Harunaga, Jill S.;Yamada, Kenneth M.
通讯作者：
Yamada, Kenneth M.
影响因子：
5
作者：
Fukazawa, R;Miller, TA;Sawyer, DB
通讯作者：
Sawyer, DB