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人类诱导的多能干细胞衍生纳米纤维用于心肌细胞保护和增殖

Yuhua Wei¹, Xiaoxiao Geng¹, Qing You²

¹Department of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, 1190742, Singapore.

Bioactive materials

|June 2, 2025

概括

这项研究开发了基因编辑干细胞的低免疫性纳米纤维,以促进心脏修复. 这些纳米纤维增强心肌细胞的存活和增殖,提供了损伤后心脏再生的潜力.

科学领域:

再生医学是一种再生医学.
心血管生物学心血管生物学
干细胞疗法是一种干细胞疗法.

背景情况:

成人哺乳动物心肌细胞 (CMs) 的细胞循环活动有限,阻碍心脏修复.
开发重新激活CM细胞周期的策略对于心脏再生至关重要.

研究的目的:

从工程人类诱导的多能干细胞 (hiPSCs) 来制造低免疫性纳米纤维 (NVs),用于心脏保护和再生.
研究这些NVs在促进心肌细胞存活,增殖和心脏功能损伤后的治疗潜力.

主要方法:

通过使用CRISPR/Cas9.9敲除β2-微型球蛋白,生成一个低免疫原性hiPSC线 (B2MKO-hiPSCs).
制造了B2MKO-hiPSC衍生的纳米纤维 (B2MKO-hiPSC-NVs),并分析了它们的蛋白质载荷.
给B2MKO-hiPSC-NVs用于hiPSC衍生的CM和心脏缺血症/再输液损伤的小鼠模型.

主要成果:

B2MKO-hiPSC-NVs被丰富了调节细胞循环和清除活性氧物种 (ROS) 的蛋白质.
NV 治疗减少了 CM 亡,防止氧化应激,并通过 AKT 和 YAP 途径增加了扩散.
在体内研究表明,治疗小鼠的心脏功能得到改善,心脏病发作大小减少,CM存活率和细胞循环活性提高.

结论:

B2MKO-hiPSC-NVs具有低免疫原性质,并提供促进心脏保护和再生的治疗载荷.
NV货物激活AKT和YAP通路,清除ROS,并刺激CM细胞循环活动,显示出治疗心脏损伤的巨大潜力.

关键词:

细胞循环的细胞周期肌心脏保护肌心脏的保护纳米纤维是如何形成的多能干细胞是多能干细胞.再生再生再生的过程

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