College of Stomatology, Chongqing Medical University, Chongqing 401147, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing 401147, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, China.
College of Stomatology, Chongqing Medical University, Chongqing 401147, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing 401147, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, China.
J Adv Res. 2023 Mar;45:15-29. doi: 10.1016/j.jare.2022.05.012. Epub 2022 May 31.
Mesenchymal stromal/stem cells (MSCs) are the most promising stem cells for the treatment of multiple inflammatory and immune diseases due to their easy acquisition and potent immuno-regulatory capacities. These immune functions mainly depend on the MSC secretion of soluble factors. Recent studies have shown that the metabolism of MSCs plays critical roles in immunomodulation, which not only provides energy and building blocks for macromolecule synthesis but is also involved in the signaling pathway regulation.
A thorough understanding of metabolic regulation in MSC immunomodulatory properties can provide new sights to the enhancement of MSC-based therapy.
MSC immune regulation can be affected by cellular metabolism (glucose, adenosine triphosphate, lipid and amino acid metabolism), which further mediates MSC therapy efficiency in inflammatory and immune diseases. The enhancement of glycolysis of MSCs, such as signaling molecule activation, inflammatory cytokines priming, or environmental control can promote MSC immune functions and therapeutic potential. Besides glucose metabolism, inflammatory stimuli also alter the lipid molecular profile of MSCs, but the direct link with immunomodulatory properties remains to be further explored. Arginine metabolism, glutamine-glutamate metabolism and tryptophan-kynurenine via indoleamine 2,3-dioxygenase (IDO) metabolism all contribute to the immune regulation of MSCs. In addition to the metabolism dictating the MSC immune functions, MSCs also influence the metabolism of immune cells and thus determine their behaviors. However, more direct evidence of the metabolism in MSC immune abilities as well as the underlying mechanism requires to be uncovered.
间充质基质/干细胞（MSCs）由于易于获取和强大的免疫调节能力，是治疗多种炎症和免疫疾病最有前途的干细胞。这些免疫功能主要取决于 MSC 的可溶性因子分泌。最近的研究表明，MSC 的代谢在免疫调节中起着关键作用，它不仅为大分子合成提供能量和构建块，还参与信号通路的调节。
深入了解 MSC 免疫调节特性中的代谢调控，可以为增强基于 MSC 的治疗提供新的视角。
MSC 的免疫调节可以受到细胞代谢（葡萄糖、三磷酸腺苷、脂质和氨基酸代谢）的影响，这进一步介导了 MSC 在炎症和免疫疾病中的治疗效果。增强 MSC 的糖酵解，如信号分子激活、炎症细胞因子启动或环境控制，可以促进 MSC 的免疫功能和治疗潜能。除了葡萄糖代谢，炎症刺激还改变了 MSC 的脂质分子谱，但与免疫调节特性的直接联系仍有待进一步探索。精氨酸代谢、谷氨酰胺-谷氨酸代谢和色氨酸-犬尿氨酸通过吲哚胺 2,3-双加氧酶（IDO）代谢都有助于 MSC 的免疫调节。除了代谢决定 MSC 的免疫功能外，MSC 还影响免疫细胞的代谢，从而决定其行为。然而，需要更多直接的证据来揭示代谢在 MSC 免疫能力中的作用及其潜在机制。
