研究动态
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纳米线人类心脏器官移植使梗死心脏的恢复效率和效果高度高效。

Nanowired human cardiac organoid transplantation enables highly efficient and effective recovery of infarcted hearts.

发表日期:2023 Aug 04
作者: Yu Tan, Robert C Coyle, Ryan W Barrs, Sophia E Silver, Mei Li, Dylan J Richards, Yiliang Lin, Yuanwen Jiang, Hongjun Wang, Donald R Menick, Kristine Deleon-Pennell, Bozhi Tian, Ying Mei
来源: Stem Cell Research & Therapy

摘要:

人类心脏器官样体将极大地促进心血管疾病建模和人类多能干细胞来源心肌细胞(hPSC-CM)移植的发展。在这里,我们展示了通过电子导电硅纳米线(e-SiNWs)工程化的心脏器官样体显著增强了hPSC-CM治疗梗塞心脏的疗效。我们首先证明了e-SiNWs的生物相容性及其改善健康大鼠心肌微组织移植的能力。随后,将人类心脏器官样体与hPSC-CMs、非肌细胞支持细胞和e-SiNWs一起进行工程化。非肌细胞支持细胞增加了心脏器官样体对缺血的耐受性,而e-SiNWs显著改善了电传导能力。在移植入缺血/再灌注损伤的大鼠心脏后,纳米线心脏器官样体显著提高了移植的hPSC-CMs的收缩发展,诱导了强效的心脏功能恢复,并减少了不适应性左心室重塑。与相同损伤模型下的现代研究相比,使用20倍更低剂量的hPSC-CMs实现了更好的功能恢复,揭示了导电纳米材料和人类心脏器官样体在高效心脏修复方面的治疗协同作用。
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.