Metabolic Switching of Cultured Mesenchymal Stem Cells Creates Super Mitochondria in Rescuing Ischemic Neurons.

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2023-03-01 DOI:10.1007/s12017-022-08720-3

Anna Gorsky, Molly Monsour, Hung Nguyen, Vanessa Castelli, Jea-Young Lee, Cesar V Borlongan

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引用次数: 5

Abstract

Transfer of healthy mitochondria from mesenchymal stem cells (MSCs) to ischemic neurons represents a potent stroke therapeutic. MSCs were grown under ambient conditions (nMSCs) or a metabolic switching paradigm by alternating galactose and glucose in medium (sMSCs) and then assayed for oxygen consumption rates using the Seahorse technology. Subsequently, primary neurons were subjected to oxygen glucose deprivation (OGD) and then co-cultured with either nMSCs or sMSCs. Compared to nMSCs, sMSCs displayed higher basal energy production, larger spare respiratory capacity, greater ATP production, and decreased proton leak. Co-culture of OGD-exposed neurons with sMSCs conferred greater cell viability, enhanced cell metabolism, reduced mitochondrial reactive oxidative species mRNA, and elevated mitochondria ATP mRNA than those cultured with nMSCs. Metabolic switching produces "super" mitochondria that may underlie the therapeutic benefit of using sMSCs to treat ischemic cells.

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培养间充质干细胞代谢转换产生超级线粒体在缺血性神经元的修复中的作用。

将健康线粒体从间充质干细胞(MSCs)转移到缺血性神经元是一种有效的中风治疗方法。在环境条件下(nMSCs)或通过在培养基中交替使用半乳糖和葡萄糖(sMSCs)的代谢转换模式培养MSCs，然后使用Seahorse技术检测氧消耗率。随后，将原代神经元进行氧葡萄糖剥夺(OGD)，然后与nMSCs或sMSCs共培养。与nMSCs相比，sMSCs显示出更高的基础能量产生、更大的备用呼吸能力、更多的ATP产生和更少的质子泄漏。与nMSCs共培养相比，ogd暴露的神经元与sMSCs共培养具有更高的细胞活力，增强细胞代谢，降低线粒体活性氧化物种mRNA，并提高线粒体ATP mRNA。代谢开关产生“超级”线粒体，这可能是使用sMSCs治疗缺血性细胞的治疗益处的基础。

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