Metabolic profile of mesenchymal stromal cells and macrophages in the presence of polyethylene particles in a 3D model.
Metabolic profile of mesenchymal stromal cells and macrophages in the presence of polyethylene particles in a 3D model.
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DOI：
10.1186/s13287-023-03260-4
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发表时间：
2023-04-21
影响因子：
7.5
通讯作者：
中科院分区：
文献类型：
--
作者：
MSC和巨噬细胞之间的持续串扰是由污染的聚乙烯颗粒（cPE）引起的急性和慢性炎症的组成部分;然而，这种炎症微环境对线粒体代谢的影响尚未完全阐明。我们假设（a）暴露于cPE导致线粒体代谢和糖酵解重编程受损，（B）巨噬细胞在该途径中发挥关键作用。 我们在三维明胶甲基丙烯酸酯（3D GelMA）构建体/支架中培养了具有/不具有未定型M0巨噬细胞、具有/不具有cPE的MSC。我们评估了线粒体功能（膜电位和活性氧-ROS产生），三磷酸腺苷（ATP）产生的代谢途径（糖酵解或氧化磷酸化）和对应激机制的反应。我们还研究了巨噬细胞向促炎M1或抗炎M2表型的极化以及MSC的成骨分化。 暴露于cPE损害了MSC的线粒体代谢;添加M0巨噬细胞恢复了健康的线粒体功能。暴露于cPE诱导的糖酵解重编程的巨噬细胞，但也启动了对这种应激的反应，以恢复线粒体生物合成和稳态氧化磷酸化。与MSC共培养的未定型M0巨噬细胞极化为M1和M2表型。21天后，各组之间的骨生成相当。 这项工作证实，在MSC和巨噬细胞的3D共培养模型中，cPE暴露会引发线粒体代谢受损和糖酵解重编程，并证明与MSC共培养的巨噬细胞会发生代谢变化，以维持能量产生并恢复稳态代谢。
Continuous cross talk between MSCs and macrophages is integral to acute and chronic inflammation resulting from contaminated polyethylene particles (cPE); however, the effect of this inflammatory microenvironment on mitochondrial metabolism has not been fully elucidated. We hypothesized that (a) exposure to cPE leads to impaired mitochondrial metabolism and glycolytic reprogramming and (b) macrophages play a key role in this pathway. We cultured MSCs with/without uncommitted M0 macrophages, with/without cPE in 3-dimensional gelatin methacrylate (3D GelMA) constructs/scaffolds. We evaluated mitochondrial function (membrane potential and reactive oxygen species—ROS production), metabolic pathways for adenosine triphosphate (ATP) production (glycolysis or oxidative phosphorylation) and response to stress mechanisms. We also studied macrophage polarization toward the pro-inflammatory M1 or the anti-inflammatory M2 phenotype and the osteogenic differentiation of MSCs. Exposure to cPE impaired mitochondrial metabolism of MSCs; addition of M0 macrophages restored healthy mitochondrial function. Macrophages exposed to cPE-induced glycolytic reprogramming, but also initiated a response to this stress to restore mitochondrial biogenesis and homeostatic oxidative phosphorylation. Uncommitted M0 macrophages in coculture with MSC polarized to both M1 and M2 phenotypes. Osteogenesis was comparable among groups after 21 days. This work confirmed that cPE exposure triggers impaired mitochondrial metabolism and glycolytic reprogramming in a 3D coculture model of MSCs and macrophages and demonstrated that macrophages cocultured with MSCs undergo metabolic changes to maintain energy production and restore homeostatic metabolism.
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影响因子：
14
作者：
Nichol, Jason W.;Koshy, Sandeep T.;Bae, Hojae;Hwang, Chang M.;Yamanlar, Seda;Khademhosseini, Ali
通讯作者：
Khademhosseini, Ali
影响因子：
23.9
作者：
Caplan AI;Correa D
通讯作者：
Correa D
影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
DOI：
10.1164/rccm.201701-0170oc
发表时间：
2017-11-15
影响因子：
24.7
作者：
Morrison, Thomas J.;Jackson, Megan V.;Krasnodembskaya, Anna D.
通讯作者：
Krasnodembskaya, Anna D.
影响因子：
2.8
作者：
Courtnay, Rupert;Ngo, Darleen C.;Karagiannis, Tom C.
通讯作者：
Karagiannis, Tom C.