Wei Yunpeng, Yang Jingzhao, Zu Wenhong, Wang Mengran, Zhao Yong
Faculty of Synthetic Biology, Shenzhen University of Advanced Technology, Shenzhen 518107, China.
CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
J Immunol Res. 2025 Apr 28;2025:9994439. doi: 10.1155/jimr/9994439. eCollection 2025.
Macrophages play essential roles in homeostasis and disease, and they were considered terminally differentiated cells that cannot proliferate. However, growing evidence shows that macrophages can self-renew in homeostasis and multiple pathological states in vivo and artificial induction in vitro. With the rise of immune cell therapy based on macrophages, large-scale in vitro expansion of macrophages has become more and more urgent. However, the proliferation of macrophages in vitro is still inefficient because of the heterogeneity of macrophages, complicated crosstalk between macrophages and their microenvironments, and poor understanding of macrophage proliferation regulations. In this review, we summarized the discoveries known to stimulate macrophage proliferation in vitro, including cytokines, small molecule compounds, metabolites, the composition of pathogens and apoptotic cells, natural product extracts, gene editing, and other factors, as well as related mechanisms. It can be concluded that the promotion of macrophage proliferation in vitro covers various approaches and mechanisms. However, it is still necessary to test more strategies and learn more macrophage proliferation mechanisms to achieve large-scale engineering expansion of macrophages in vitro.
巨噬细胞在体内稳态和疾病中发挥着重要作用，它们曾被认为是终末分化细胞，无法增殖。然而，越来越多的证据表明，巨噬细胞在体内稳态、多种病理状态以及体外人工诱导下都能够自我更新。随着基于巨噬细胞的免疫细胞疗法的兴起，巨噬细胞的大规模体外扩增变得越来越迫切。然而，由于巨噬细胞的异质性、巨噬细胞与其微环境之间复杂的相互作用以及对巨噬细胞增殖调控的了解不足，巨噬细胞在体外的增殖效率仍然较低。在这篇综述中，我们总结了已知的能够刺激巨噬细胞体外增殖的发现，包括细胞因子、小分子化合物、代谢产物、病原体和凋亡细胞的组成成分、天然产物提取物、基因编辑等因素以及相关机制。可以得出结论，促进巨噬细胞体外增殖涵盖了多种方法和机制。然而，仍有必要测试更多策略并深入了解更多巨噬细胞增殖机制，以实现巨噬细胞在体外的大规模工程化扩增。
