Li Youyuan, Wang Hong, Li Zhilei, Wang Huichao, Gao Yi, Wu Chaoran, Wei Bangguo, Guo Zhanyun, Wang Xijin, Jing Guoxin, Wang Shilong
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, PR China.
Department of Neurology, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, PR China.
Mater Today Bio. 2025 Jul 7;33:102042. doi: 10.1016/j.mtbio.2025.102042. eCollection 2025 Aug.
In the cultivation of mouse embryonic stem cells (mESCs), leukemia inhibitory factor (LIF) and mitotically inactive mouse embryonic fibroblasts (MEFs) are usually used to maintain the self-renewal and pluripotency of mESCs. However, the high cost of LIF and the immunogenicity of MEFs limit their clinical application in stable culture and large-scale expansion of mESCs. Therefore, it is necessary to pursue a low-cost, convenient, and safe alternative. This study found that Fe-doped metal organic framework nanoparticles (Fe MOF) have good biocompatibility under long-term cultivation and could maintain the self-renewal of mESCs in the absence of LIF and MEFs, without destroying the potential of mESCs to differentiate into three germ layer cells. Through transcriptome sequencing, it was demonstrated that Fe MOF nanomaterials could not only upregulate the expression of LIFR/GP130, but more importantly, they could activate the Fe mediated BMP4/ALK/SMAD signaling pathway. The experimental results indicate that Fe MOF nanomaterials could effectively maintain the self-renewal and pluripotency of mESCs. This study demonstrates that Fe MOF could not only replace the LIF factor, but also has a stronger ability to promote the self-renewal of mESCs owe to its multi-signal pathway regulation function, providing application prospects in the in vitro cultivation of mESCs.
在小鼠胚胎干细胞（mESCs）的培养中，白血病抑制因子（LIF）和有丝分裂失活的小鼠胚胎成纤维细胞（MEFs）通常用于维持mESCs的自我更新和多能性。然而，LIF的高成本和MEFs的免疫原性限制了它们在mESCs稳定培养和大规模扩增中的临床应用。因此，有必要寻求一种低成本、方便且安全的替代方法。本研究发现，铁掺杂金属有机框架纳米颗粒（Fe MOF）在长期培养下具有良好的生物相容性，并且在没有LIF和MEFs的情况下能够维持mESCs的自我更新，而不会破坏mESCs分化为三个胚层细胞的潜能。通过转录组测序表明，Fe MOF纳米材料不仅可以上调LIFR/GP130的表达，更重要的是，它们可以激活铁介导的BMP4/ALK/SMAD信号通路。实验结果表明，Fe MOF纳米材料能够有效地维持mESCs的自我更新和多能性。本研究表明，Fe MOF不仅可以替代LIF因子，而且由于其多信号通路调节功能，具有更强的促进mESCs自我更新的能力，为mESCs的体外培养提供了应用前景。
