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

Abstract

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.

Injectable and Conductive Nanomicelle Hydrogel with α-Tocopherol Encapsulation for Enhanced Myocardial Infarction Repair

“…Quantitative analysis revealed the highest number of newly formed blood vessels in the FPDA group, indicating a greater degree of myocardial injury recovery following myocardial infarction (Figure b,c). This may be attributed to the ability of the conductive hydrogel to recruit endothelial cells to migrate to the infarcted area, and during the process of myocardial infarction repair, the FPDA hydrogel reduced inflammation in the infarcted area, creating a favorable cardiac microenvironment conducive to endothelial cell growth, thereby promoting neovascularization. ,, …”

“…This may be attributed to the ability of the conductive hydrogel to recruit endothelial cells to migrate to the infarcted area, and during the process of myocardial infarction repair, the FPDA hydrogel reduced inflammation in the infarcted area, creating a favorable cardiac microenvironment conducive to endothelial cell growth, thereby promoting neovascularization. 8,43,44…”

The new era of cardiovascular research: revolutionizing cardiovascular research with 3D models in a dish

“…While cardiac spheroids offer significant potential for restoring the cardiac function of infarcted hearts, the relatively immature phenotype of hiPSC-CMs usually results in unsynchronized contraction, potentially increasing the risk of arrhythmias [ 152 , 153 ]. To overcome this challenge, electrically conductive materials and multiple cell types can be incorporated into cardiac spheroids [ 154 , 155 ]. For example, incorporating silicon nanowires into cardiac spheroids containing hPSC-CMs, CFs, ECs, and stromal cells markedly improves therapeutic angiogenesis in ischemic tissues, leading to a significant increase in cell retention and survival [ 154 ].…”

“…To overcome this challenge, electrically conductive materials and multiple cell types can be incorporated into cardiac spheroids [ 154 , 155 ]. For example, incorporating silicon nanowires into cardiac spheroids containing hPSC-CMs, CFs, ECs, and stromal cells markedly improves therapeutic angiogenesis in ischemic tissues, leading to a significant increase in cell retention and survival [ 154 ]. In addition to CMs, vascular cells also have a pivotal role in cell regeneration.…”

Protection of Si Nanowires against Aβ Toxicity by the Inhibition of Aβ Aggregation

“…As far as the bio domains are considered, Si NWs are widely studied. For example, the design of conductive Si NW for cardiac-like organs significantly enhanced the therapeutic effect of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) in treating infarcted hearts [33]. In terms of drug delivery, Peng et al utilized a freestanding Si NW with a diameter of about 100 nm and a length of about 500 nm to load the anticancer drug DOX [34].…”