Au@Pt Nanoparticles Enhance Maturation and Contraction of Mouse Embryonic Stem Cells-Derived and Neonatal Mouse Cardiomyocytes.

IF 4.4 4区 医学 Q2 CELL & TISSUE ENGINEERING
Shuai Dong, Kangli Guo, Nana Zhao, Yan Xu
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引用次数: 0

Abstract

Background: Cardiomyocytes derived from pluripotent stem cells (PSCs) hold great promise in heart damage repair in vivo and drug screening in vitro. However, PSC-derived cardiomyocytes exhibit immature structural and functional properties, which hinder their widespread application. To address this challenge, we designed bimetallic gold-platinum nanoparticles (Au@Pt NPs) endowed with intrinsic oxidase-like, peroxidase-like, and catalase-like activities and high electrical conductivity for promoting cardiomyocyte maturation.

Methods: Mouse embryonic stem cell (ESC)-derived and neonatal mouse cardiomyocytes were used to evaluate the effects of Au@Pt NPs on cardiomyocyte maturation. The expression and alignment of cardiomyocyte myofibril proteins were analyzed by qRT-PCR, western blot, and immunofluorescence staining. Cellular functionality was analyzed by the multi-electrode array.

Results: By adding Au@Pt NPs at different stages of cardiac differentiation of mouse ESCs, we found that treatment with Au@Pt NPs at the late stage could promote the maturation of differentiated cardiomyocytes, evidenced by increased expression of mature myofibril protein isoforms, more aligned myofibrils, and enhanced sarcomere length. Additionally, Au@Pt NPs can enhance the expression of mature sarcomere components, increase sarcomere length, and significantly boost beating amplitude and conduction velocity in neonatal mouse cardiomyocytes. Furthermore, Au@Pt NPs promoted cell cycle arrest, increased intracellular reactive oxygen species levels, and promoted contractility by inducing the ERK1/2 signaling pathway.

Conclusion: Our results indicate that the bimetallic Au@Pt NPs with intrinsic oxidase-like, peroxidase-like, and catalase-like activities and high electrical conductivity could promote the maturation of ESCs-derived and neonatal mouse cardiomyocytes, providing a promising approach for cardiomyocyte maturation and cell therapy for cardiovascular disease.

Au@Pt纳米颗粒促进小鼠胚胎干细胞来源和新生小鼠心肌细胞的成熟和收缩。
背景:多能干细胞(PSCs)衍生的心肌细胞在体内心脏损伤修复和体外药物筛选方面具有广阔的应用前景。然而,psc衍生的心肌细胞表现出不成熟的结构和功能特性,这阻碍了它们的广泛应用。为了解决这一挑战,我们设计了双金属金-铂纳米颗粒(Au@Pt NPs),该纳米颗粒具有内在的氧化酶样、过氧化物酶样和过氧化氢酶样活性,并具有高导电性,可促进心肌细胞成熟。方法:采用小鼠胚胎干细胞(ESC)源性心肌细胞和新生小鼠心肌细胞评价Au@Pt NPs对心肌细胞成熟的影响。采用qRT-PCR、western blot和免疫荧光染色分析心肌细胞肌原纤维蛋白的表达和序列。采用多电极阵列分析细胞功能。结果:通过在小鼠ESCs心脏分化的不同阶段添加Au@Pt NPs,我们发现Au@Pt NPs在后期处理可以促进分化心肌细胞的成熟,表现为成熟肌原纤维蛋白亚型表达增加,肌原纤维排列更整齐,肌节长度增加。此外,Au@Pt NPs可以增强成熟肌节成分的表达,增加肌节长度,显著提高新生小鼠心肌细胞的搏动幅度和传导速度。此外,Au@Pt NPs促进细胞周期阻滞,增加细胞内活性氧水平,并通过诱导ERK1/2信号通路促进收缩性。结论:我们的研究结果表明,具有内在氧化酶样、过氧化物酶样和过氧化氢酶样活性和高电导率的双金属Au@Pt NPs可以促进escs衍生和新生小鼠心肌细胞的成熟,为心肌细胞成熟和心血管疾病的细胞治疗提供了一种有前景的途径。
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来源期刊
Tissue engineering and regenerative medicine
Tissue engineering and regenerative medicine CELL & TISSUE ENGINEERING-ENGINEERING, BIOMEDICAL
CiteScore
6.80
自引率
5.60%
发文量
83
审稿时长
6-12 weeks
期刊介绍: Tissue Engineering and Regenerative Medicine (Tissue Eng Regen Med, TERM), the official journal of the Korean Tissue Engineering and Regenerative Medicine Society, is a publication dedicated to providing research- based solutions to issues related to human diseases. This journal publishes articles that report substantial information and original findings on tissue engineering, medical biomaterials, cells therapy, stem cell biology and regenerative medicine.
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