捐赠者的年龄会影响hiPSC衍生的内皮原体的血管生成潜力
Bryce Larsen1, Cody Callahan1, Arshitha Rayanki1
1Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78751, USA.
bioRxiv : the preprint server for biology
|July 16, 2025
概括
供体年龄显著影响用于血管再生的人类诱导多能干细胞 (hiPSCs) 的功能. 成熟的捐赠者hiPSC衍生的内皮原体表现出血管结构形成的减少,这对治疗老年患者构成了挑战.
科学领域:
- 干细胞生物学 干细胞生物学
- 血管再生 血管再生
- 衰老的研究研究.
背景情况:
- 人类诱导的多能干细胞 (hiPSCs) 显示出血管再生的潜力.
- 临床应用需要来自老年人的细胞,但它们对hiPSC衍生的内皮原体 (hiPSC-EPs) 的影响尚不清楚.
研究的目的:
- 调查捐赠者年龄对hiPSC-EPs血管再生功能的影响.
主要方法:
- hiPSC-EPs来自新生儿 (ND) 和成熟 (MD) 捐赠者.
- 进行了功能,表观遗传和转录组分析.
- 在3D水凝和2D培养中评估了血管结构的形成.
主要成果:
- 与ND-hiPSC-EPs相比,MD-hiPSC-EPs产生了更高的CD34+细胞,但形成了与ND-hiPSC-EPs相比相互连接较差,非发光的血管结构.
- MD-hiPSC-EPs在2D培养中显示细胞密度降低和异常VE-Cadherin局部化.
- 表观遗传年龄预测表明MD-hiPSC-EPs具有更先进的发育特征,与减少血管生成能力相关.
结论:
- 捐赠者的年龄显著改变hiPSC-EP血管功能.
- 在基于hiPSC的血管工程中,考虑供体年龄至关重要.
- 在hiPSC-EPs中,与年龄相关的功能衰退对老年人群的治疗转化构成障碍.
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