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用患者特异性诱导的多能干细胞建模糖尿病内皮功能障碍

Rayyan Gorashi^1,2, Nancy Rivera-Bolanos^1,2, Caitlyn Dang³

¹Department of Biomedical Engineering Northwestern University Evanston and Chicago Illinois USA.

Bioengineering & translational medicine

|November 29, 2023

概括

人类干细胞衍生的内皮细胞模型糖尿病功能障碍,揭示遗传和环境因素. 这种方法确定了糖尿病个性化心血管护理的潜在药物治疗方法.

科学领域:

心血管生物学心血管生物学
代谢障碍代谢障碍代谢障碍
干细胞生物学干细胞生物学

背景情况:

糖尿病显著增加心血管疾病的风险,主要是通过内皮功能障碍.
现有的体外模型很难捕捉糖尿病内皮功能障碍中遗传和环境因素的复杂相互作用.
人类诱导多能干细胞 (iPSC) 衍生的内皮细胞 (ECs) 为开发更全面的疾病模型提供了一个有前途的途径.

研究的目的:

开发和验证糖尿病内皮功能障碍的体外模型,使用患者衍生和健康的iPSC-EC.
调查遗传背景和糖尿病引起的环境因素对内皮细胞功能的影响.
利用这些模型来选糖尿病心血管并发症的潜在治疗剂.

主要方法:

从糖尿病患者和健康对照人群的人类iPSC细胞系生成内皮细胞.
在标准和糖尿病原性模仿条件下培养iPSC-ECs.
全转录组RNA测序 (RNA-seq) 用于分析基因表达特征.
血管激素受体阻断剂 (ARB) 的体外查,以确定其治疗疗效.

主要成果:

来自糖尿病患者的iPSC-ECs表现出一个重复的糖尿病表型,独立于培养环境.
暴露于糖尿病性疾病导致健康iPSC-EC的功能障碍,但没有改变已经功能障碍的糖尿病iPSC-EC.
RNA-seq发现了健康和糖尿病iPSC-ECs之间的显著转录组范围的差异.
基于iPSC的模型成功地确定了患者特异性的ARBs,这些ARB在体外改善了内皮功能.

结论:

从iPSC衍生的内皮细胞为研究糖尿病内皮功能障碍提供了强大的体外模型,结合了遗传和环境影响.
这些模型为糖尿病相关心血管并发症的病理生理学提供了宝贵的见解.
iPSC技术在个性化医疗和糖尿病治疗中加速药物发现方面具有显著的潜力.

关键词:

心血管疾病心血管疾病在糖尿病中,糖尿病是血糖类的.疾病建模疾病建模药物查对药物进行查.它们是内皮细胞的内皮细胞.诱导多能干细胞的诱导干细胞.

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