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人诱导多能干细胞源性星形胶质细胞和胎鼠原代星形胶质细胞的代谢评估:乳酸和葡萄糖代谢。

Metabolic Assessment of Human Induced Pluripotent Stem Cells-Derived Astrocytes and Fetal Primary Astrocytes: Lactate and Glucose Turnover.

机构信息

Division of Micro and Nanosystems, Department of Intelligent Systems, School of Electrical Engineering and Computer Science, KTH Royal Institute of Technology, 10044 Stockholm, Sweden.

CVRM Safety, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, 43150 Gothenburg, Sweden.

出版信息

Biosensors (Basel). 2022 Oct 8;12(10):839. doi: 10.3390/bios12100839.

Abstract

Astrocytes represent one of the main cell types in the brain and play a crucial role in brain functions, including supplying the energy demand for neurons. Moreover, they are important regulators of metabolite levels. Glucose uptake and lactate production are some of the main observable metabolic actions of astrocytes. To gain insight into these processes, it is essential to establish scalable and functional sources for in vitro studies of astrocytes. In this study, we compared the metabolic turnover of glucose and lactate in astrocytes derived from human induced pluripotent stem cell (hiPSC)-derived Astrocytes (hiAstrocytes) as a scalable astrocyte source to human fetal astrocytes (HFAs). Using a user-friendly, commercial flow-based biosensor, we could verify that hiAstrocytes are as glycogenic as their fetal counterparts, but their normalized metabolic turnover is lower. Specifically, under identical culture conditions in a defined media, HFAs have 2.3 times higher levels of lactate production compared to hiAstrocytes. In terms of glucose, HFAs have 2.1 times higher consumption levels than hiAstrocytes at 24 h. Still, as we describe their glycogenic phenotype, our study demonstrates the use of hiAstrocytes and flow-based biosensors for metabolic studies of astrocyte function.

摘要

星形胶质细胞是大脑中的主要细胞类型之一,在大脑功能中起着至关重要的作用,包括为神经元提供能量需求。此外,它们是代谢物水平的重要调节剂。葡萄糖摄取和乳酸生成是星形胶质细胞的一些主要可观察代谢作用。为了深入了解这些过程,必须建立可扩展的体外星形胶质细胞研究的功能来源。在这项研究中,我们将源自人诱导多能干细胞 (hiPSC) 的星形胶质细胞 (hiAstrocytes) 的代谢周转率与作为可扩展星形胶质细胞来源的人胎星形胶质细胞 (HFAs) 进行了比较。使用用户友好的商业流式生物传感器,我们可以验证 hiAstrocytes 与它们的胎鼠对应物一样具有糖生成能力,但它们的归一化代谢周转率较低。具体来说,在相同的培养条件下,在定义的培养基中,与 hiAstrocytes 相比,HFAs 的乳酸生成水平高 2.3 倍。就葡萄糖而言,HFAs 在 24 小时内的消耗水平比 hiAstrocytes 高 2.1 倍。尽管如此,正如我们描述的它们的糖生成表型一样,我们的研究表明了 hiAstrocytes 和流式生物传感器在星形胶质细胞功能的代谢研究中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83da/9599592/ac4d1fd8de51/biosensors-12-00839-g001.jpg

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