针对非侵入性治疗药物发现的脂肪芯片模型的优化和验证
Lindsey K Huff1, Charles M Amurgis2, Lauren E Kokai3
1Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, United States.
Frontiers in bioengineering and biotechnology
|July 11, 2024
概括
使用初级脂肪细胞的新型脂肪芯片模型有效地模仿了人类脂肪组织的反应. 这种工程模型可以持续监测脂肪细胞功能和胰岛素反应,有助于发现治疗肥胖和II型糖尿病 (T2D) 的药物.
科学领域:
- 生物医学工程 生物医学工程
- 细胞生物学 细胞生物学
- 代谢性疾病研究研究
背景情况:
- 肥胖是一个主要的公共卫生问题,与II型糖尿病 (T2D),心脏病和癌症等严重的并发症有关.
- 脂肪组织在疾病发展中起着至关重要的作用,需要研究和药物发现的先进模型.
- 工程组织模型对于理解疾病机制和评估治疗干预措施至关重要.
研究的目的:
- 用初级成熟脂肪细胞验证一种新的芯片上的脂肪 (FOAC) 模型.
- 建立一个可复制的平台来研究脂肪细胞的功能和对刺激的反应.
- 为了使脂肪细胞代谢活性和胰岛素敏感性的持续,非侵入性监测.
主要方法:
- 开发和验证使用Micronit perfusion设备与初级成熟脂肪细胞的FOAC模型.
- 实施非侵入性读取技术:对代谢活动和葡萄糖吸收测量进行resazurin测定.
- 在工程微环境中,描述脂肪细胞的行为,包括高缩和胰岛素介导的葡萄糖摄取.
主要成果:
- 基于Micronit的FOAC模型证明了可重复性,并保持了脂肪细胞活力,代谢活性和功能.
- 该模型成功地模仿了生理上相关的反应,包括脂肪细胞缩和胰岛素介导的葡萄糖摄取.
- 发现脂肪细胞大小调节取决于细胞外矩阵特性,在氨酸水凝中实现一致的大小,无论细胞的初始大小如何.
结论:
- 经过验证的FOAC模型作为研究脂肪组织生物学和疾病的强大平台.
- 该模型适用于研究II型糖尿病 (T2D) 和监测脂肪细胞对胰岛素的反应.
- 该FOAC系统有助于对针对代谢障碍的新型药物的治疗疗效进行纵向跟踪.
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