从人类多能干细胞中特定诱导右心室类心肌细胞
Yukihiro Saito1, Kazufumi Nakamura2,3, Yuki Katanosaka4,5,6
1Department of Cardiovascular Medicine, Okayama University Hospital, Okayama, Japan. p5438a3l@s.okayama-u.ac.jp.
Stem cell research & therapy
|September 27, 2025
概括
研究人员开发了一种方法,可以从人类多能干细胞 (hPSC) 产生右心室样心肌细胞. 这一进步允许研究室特异性心肌细胞差异,并支持疾病建模研究.
科学领域:
- 心血管生物学 心血管生物学
- 干细胞分化的过程
- 发展生物学 发展生物学
背景情况:
- 人类多能干细胞衍生心肌细胞 (hPSC-CMs) 需要用于应用的室特异性表征.
- 显著的第一心场 (FHF) 和第二心场 (SHF) 的原始细胞群分别产生左心室 (LV) 和右心室 (RV) 的心肌细胞.
- 在hPSC衍生的LV类心肌细胞和RV类心肌细胞之间的表型差异尚不清楚.
研究的目的:
- 开发有效的策略,使人类多能干细胞 (hPSCs) 分化为室内特异性心肌细胞.
- 为了研究hPSC衍生LV类和RV类心肌细胞之间的潜在的表型差异.
主要方法:
- 修改了GiWi协议 (GSK3β抑制接着Wnt抑制) 用于hPSC心脏分化.
- 在中皮形成期间添加胰岛素或BMP抗剂以调节信号通路.
- 评估了FHF和SHF标志物的心脏前代种群,并对室内特定标志物的差异化hPSC-CMs进行了表征.
主要成果:
- 标准的GiWi协议主要产生了类似FHF的原始细胞和类似LV的心肌细胞.
- 在介质体诱导过程中抑制BMP信号传递将原始种群转移到SHF类特征.
- 与LV类细胞相比,来自SHF类祖先的hPSC-CMs表现出类似RV的基因表达模式和独特的功能性质 (收缩率,Ca2+过渡体,细胞大小).
结论:
- 建立了一个生成类似RV的hPSC-CMs的方法.
- 这种方法支持使用室特定hPSC-CMs的疾病建模研究.
- 在hPSC衍生的LV类和RV类心肌细胞之间展示了表型差异.
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