Nanowired human cardiac organoid transplantation enables highly efficient and effective recovery of infarcted hearts.
Nanowired human cardiac organoid transplantation enables highly efficient and effective recovery of infarcted hearts.
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DOI：
10.1126/sciadv.adf2898
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发表时间：
2023-08-04
期刊：
影响因子：
13.6
通讯作者：
Mei, Ying
中科院分区：
文献类型：
--
作者：
Tan, Yu;Coyle, Robert C.;Barrs, Ryan W.;Silver, Sophia E.;Li, Mei;Richards, Dylan J.;Lin, Yiliang;Jiang, Yuanwen;Wang, Hongjun;Menick, Donald R.;Deleon-Pennell, Kristine;Tian, Bozhi;Mei, Ying
人类心脏类器官在心血管疾病建模和人类多能干细胞衍生的心肌细胞（hPSC-CM）移植方面具有显着的潜力。在这里，我们展示了用导电硅纳米线（e-SiNW）工程化的心脏类器官显著增强了hPSC-CM治疗梗死心脏的疗效。我们首先证明了e-SiNW的生物相容性及其改善健康大鼠心肌中心脏微组织植入的能力。然后用hPSC-CM、非肌细胞支持细胞和e-SiNW工程化纳米毛人类心脏类器官。非肌细胞支持细胞促进了心脏类器官更大的缺血耐受性，e-SiNWs显着提高了电起搏能力。移植到缺血/再灌注损伤的大鼠心脏后，移植的心脏类器官显著改善了移植的hPSC-CM的收缩发育，诱导了有效的心脏功能恢复，并减少了适应不良的左心室重构。与具有相同损伤模型的当代研究相比，使用低20倍剂量的hPSC-CM实现了更大的功能恢复，揭示了导电纳米材料与人类心脏类器官之间的治疗协同作用，以实现有效的心脏修复。导电硅纳米线增强了用于心脏修复的工程化人类心脏微组织的治疗功效。
Human cardiac organoids hold remarkable potential for cardiovascular disease modeling and human pluripotent stem cell–derived cardiomyocyte (hPSC-CM) transplantation. Here, we show cardiac organoids engineered with electrically conductive silicon nanowires (e-SiNWs) significantly enhance the therapeutic efficacy of hPSC-CMs to treat infarcted hearts. We first demonstrated the biocompatibility of e-SiNWs and their capacity to improve cardiac microtissue engraftment in healthy rat myocardium. Nanowired human cardiac organoids were then engineered with hPSC-CMs, nonmyocyte supporting cells, and e-SiNWs. Nonmyocyte supporting cells promoted greater ischemia tolerance of cardiac organoids, and e-SiNWs significantly improved electrical pacing capacity. After transplantation into ischemia/reperfusion–injured rat hearts, nanowired cardiac organoids significantly improved contractile development of engrafted hPSC-CMs, induced potent cardiac functional recovery, and reduced maladaptive left ventricular remodeling. Compared to contemporary studies with an identical injury model, greater functional recovery was achieved with a 20-fold lower dose of hPSC-CMs, revealing therapeutic synergy between conductive nanomaterials and human cardiac organoids for efficient heart repair. Conductive silicon nanowires enhance the therapeutic efficacy of engineered human cardiac microtissues for heart repair.
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DOI：
10.1016/j.jacbts.2020.11.017
发表时间：
2021-03
期刊：
JACC. Basic to translational science
影响因子：
--
作者：
Kawaguchi S;Soma Y;Nakajima K;Kanazawa H;Tohyama S;Tabei R;Hirano A;Handa N;Yamada Y;Okuda S;Hishikawa S;Teratani T;Kunita S;Kishino Y;Okada M;Tanosaki S;Someya S;Morita Y;Tani H;Kawai Y;Yamazaki M;Ito A;Shibata R;Murohara T;Tabata Y;Kobayashi E;Shimizu H;Fukuda K;Fujita J
通讯作者：
Fujita J
影响因子：
5.9
作者：
Fernandes S;Chong JJH;Paige SL;Iwata M;Torok-Storb B;Keller G;Reinecke H;Murry CE
通讯作者：
Murry CE
影响因子：
14
作者：
Feinberg, Adam W.;Alford, Patrick W.;Jin, Hongwei;Ripplinger, Crystal M.;Werdich, Andreas A.;Sheehy, Sean P.;Grosberg, Anna;Parker, Kevin Kit
通讯作者：
Parker, Kevin Kit
影响因子：
6
作者：
Laflamme, MA;Gold, J;Murry, CE
通讯作者：
Murry, CE
影响因子：
23.9
作者：
Jgamadze, Dennis;Lim, James T.;Chen, Han-Chiao Isaac
通讯作者：
Chen, Han-Chiao Isaac