Tissue-embedded stretchable nanoelectronics reveal endothelial cell-mediated electrical maturation of human 3D cardiac microtissues.
Tissue-embedded stretchable nanoelectronics reveal endothelial cell-mediated electrical maturation of human 3D cardiac microtissues.
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组织包裹的可拉伸纳米电子学揭示了内皮细胞介导的人类3D心脏微动物的电气成熟。
DOI：
10.1126/sciadv.ade8513
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发表时间：
2023-03-10
期刊：
影响因子：
13.6
通讯作者：
Liu, Jia
中科院分区：
文献类型：
--
作者：
Lin, Zuwan;Garbern, Jessica C.;Liu, Ren;Li, Qiang;Juncosa, Estela Mancheno;Elwell, Hannah L. T.;Sokol, Morgan;Aoyama, Junya;Deumer, Undine-Sophie;Hsiao, Emma;Sheng, Hao;Lee, Richard T.;Liu, Jia
心脏病干细胞疗法的临床转化需要移植心肌细胞的电整合。电成熟的人诱导多能干细胞衍生的心肌细胞（hiPSC-CM）的产生对于电整合至关重要。在这里，我们发现hiPSC衍生的内皮细胞（hiPSC-EC）促进hiPSC-CM中选定的成熟标志物的表达。使用组织嵌入式可拉伸网状纳米电子器件，我们实现了人类三维（3D）心脏微组织电活动的长期稳定地图。结果显示，hiPSC-ECs加速了3D心脏微组织中hiPSC-CMs的电成熟。基于机器学习的心肌细胞电信号伪时间轨迹推断进一步揭示了发育过程中的电表型转变路径。在电记录数据的指导下，单细胞RNA测序确定hiPSC-EC促进具有更成熟表型的心肌细胞亚群，并且hiPSC-EC和hiPSC-CM之间的多种配体-受体相互作用上调，揭示了hiPSC-CM电成熟的协调多因素机制。总的来说，这些发现表明hiPSC-EC通过多种细胞间途径驱动hiPSC-CM电成熟。可伸展纳米电子技术跟踪与内皮细胞共培养的3D心脏微组织电成熟。
Clinical translation of stem cell therapies for heart disease requires electrical integration of transplanted cardiomyocytes. Generation of electrically matured human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) is critical for electrical integration. Here, we found that hiPSC-derived endothelial cells (hiPSC-ECs) promoted the expression of selected maturation markers in hiPSC-CMs. Using tissue-embedded stretchable mesh nanoelectronics, we achieved a long-term stable map of human three-dimensional (3D) cardiac microtissue electrical activity. The results revealed that hiPSC-ECs accelerated the electrical maturation of hiPSC-CMs in 3D cardiac microtissues. Machine learning–based pseudotime trajectory inference of cardiomyocyte electrical signals further revealed the electrical phenotypic transition path during development. Guided by the electrical recording data, single-cell RNA sequencing identified that hiPSC-ECs promoted cardiomyocyte subpopulations with a more mature phenotype, and multiple ligand-receptor interactions were up-regulated between hiPSC-ECs and hiPSC-CMs, revealing a coordinated multifactorial mechanism of hiPSC-CM electrical maturation. Collectively, these findings show that hiPSC-ECs drive hiPSC-CM electrical maturation via multiple intercellular pathways. Stretchable nanoelectronics track 3D cardiac microtissue electrical maturation with endothelial cell co-culture.
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影响因子：
38.3
作者：
通讯作者：
--
影响因子：
16.6
作者：
Dogra D;Ahuja S;Kim HT;Rasouli SJ;Stainier DYR;Reischauer S
通讯作者：
Reischauer S
影响因子：
62.1
作者：
Fang Y;Yang X;Lin Y;Shi J;Prominski A;Clayton C;Ostroff E;Tian B
通讯作者：
Tian B
影响因子：
10.5
作者：
Hoogaars, Willem M. H.;Engel, Angela;Christoffels, Vincent M.
通讯作者：
Christoffels, Vincent M.
影响因子：
48
作者：
Browaeys, Robin;Saelens, Wouter;Saeys, Yvan
通讯作者：
Saeys, Yvan