作为糖尿病血管病的模型的人类血管器官
Reiner A Wimmer1, Alexandra Leopoldi2, Martin Aichinger3
1Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria. reiner.wimmer@imba.oeaw.ac.at.
Nature
|January 18, 2019
概括
科学家从干细胞中开发出人体血管器官来研究糖尿病血管病. 这些器官模仿糖尿病血管变化,识别DLL4和NOTCH3等关键驱动因素.
科学领域:
- 生物医学工程
- 干细胞生物学
- 血管生物学
背景情况:
- 糖尿病是一种全球性流行病,
- 糖尿病血管病包括底层膜加厚和血管细胞功能障碍,但根本机制尚未完全理解.
- 内皮细胞和围细胞功能障碍与糖尿病血管病有关,但它们的确切作用尚不清楚.
研究的目的:
- 开发一种用于研究糖尿病血管病的新型体外模型.
- 研究糖尿病患者血管的结构和功能变化.
- 确定导致糖尿病血管病变的关键分子调节剂.
主要方法:
- 从多能干细胞开发自组织的3D人体血管器官.
- 将人类血管器官移植到小鼠体内,以评估血管树的形成和功能.
- 在体外和体内暴露于高血糖,炎症性细胞因子和糖尿病环境.
主要成果:
- 人体血管有机体自组成毛细血管网络与内皮细胞,细胞周细胞和底层膜.
- 在小鼠中移植的器官形成了稳定的血管树.
- 暴露于糖尿病病症导致底层膜变厚,并模仿了糖尿病患者的微血管变化.
- DLL4和NOTCH3被确定为糖尿病血管病变的关键驱动因素.
结论:
- 人类血管器官精确地概述了人体血管的结构和功能.
- 这些有机体作为一种强大的系统来模拟糖尿病血管病.
- 该研究确定DLL4和NOTCH3为关键调节剂,为糖尿病血管并发症提供潜在的治疗点.
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