成熟的人类诱导的多能干细胞衍生的心肌细胞通过α-B晶促进血管生成
Yuki Tanaka1,2, Shin Kadota3,4, Jian Zhao1
1Department of Regenerative Science and Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
Stem cell research & therapy
|September 7, 2023
概括
长期培养的人类诱导的多能干细胞衍生的心肌细胞 (hiPSC-CMs) 改善受伤的老鼠心脏的移植和成熟. 成熟的hiPSC-CMs通过α-B晶体促进血管生成,增强心脏病的治疗潜力.
科学领域:
- 心血管生物学 心血管生物学
- 再生医学是一种再生医学.
- 干细胞生物学 干细胞生物学
背景情况:
- 人类诱导的多能干细胞衍生心肌细胞 (hiPSC-CMs) 显示出治疗心脏病的前景.
- 对于有效的心脏再生的hiPSC-CMs的最佳成熟度还没有得到很好的定义.
研究的目的:
- 在大鼠心肌梗塞模型中研究长期培养成熟的hiPSC-CMs的治疗益处.
- 阐明细胞保留,移植和血管生成的增强背后的机制.
主要方法:
- 在28天 (D28-CMs) 或56天 (D56-CMs) 的时间里培养了hiPSC-CMs,并移植到心肌梗塞后的老鼠心脏中.
- 用体内成像和组织学来评估细胞保留,移植,成熟和血管生成.
- 转录基因测序和西方污点分析确定了关键的分子因素.
主要成果:
- 与D28-CMs相比,D56-CMs在移植后12周表现出高调的成熟瘤基因和优越的移植和成熟.
- 长期培养的hiPSC-CMs始终促进了微血管形成和血管生成.
- 在D56-CMs中高度表达的α-B晶体蛋白 (CRYAB) 被确定为促进内皮细胞迁移和血管生成的关键血管生成因子.
结论:
- 长期培养可以提高心脏修复的hiPSC-CMs的成熟度和治疗效果.
- 成熟的hiPSC-CMs促进了移植成熟,血管生成,并改善了移植后的心脏功能.
- 克里亚布是一种由成熟的hiPSC-CMs分泌的关键血管生成因子,突出显示了其治疗潜力.
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