Spinal cord injury (SCI) remains a severe condition with an extremely high disability rate. The challenges of SCI repair include its complex pathological mechanisms and the difficulties of neural regeneration in the central nervous system. In the past few decades, researchers have attempted to completely elucidate the pathological mechanism of SCI and identify effective strategies to promote axon regeneration and neural circuit remodeling, but the results have not been ideal. Recently, new pathological mechanisms of SCI, especially the interactions between immune and neural cell responses, have been revealed by single-cell sequencing and spatial transcriptome analysis. With the development of bioactive materials and stem cells, more attention has been focused on forming intermediate neural networks to promote neural regeneration and neural circuit reconstruction than on promoting axonal regeneration in the corticospinal tract. Furthermore, technologies to control physical parameters such as electricity, magnetism and ultrasound have been constantly innovated and applied in neural cell fate regulation. Among these advanced novel strategies and technologies, stem cell therapy, biomaterial transplantation, and electromagnetic stimulation have entered into the stage of clinical trials, and some of them have already been applied in clinical treatment. In this review, we outline the overall epidemiology and pathophysiology of SCI, expound on the latest research progress related to neural regeneration and circuit reconstruction in detail, and propose future directions for SCI repair and clinical applications.

The differentiation of neural stem cells (NSCs) into neurons is proposed to be critical in devising potential cell-based therapeutic strategies for central nervous system (CNS) diseases, however, the determination and prediction of differentiation is complex and not yet clearly established, especially at the early stage. We hypothesize that deep learning could extract minutiae from large-scale datasets, and present a deep neural network model for predictable reliable identification of NSCs fate. Remarkably, using only bright field images without artificial labelling, our model is surprisingly effective at identifying the differentiated cell types, even as early as 1 day of culture. Moreover, our approach showcases superior precision and robustness in designed independent test scenarios involving various inducers, including neurotrophins, hormones, small molecule compounds and even nanoparticles, suggesting excellent generalizability and applicability. We anticipate that our accurate and robust deep learning-based platform for NSCs differentiation identification will accelerate the progress of NSCs applications.

Leukemia inhibitory factor (LIF), an indispensable bioactive protein that sustains self‐renewal and pluripotency in stem cells, is vital for mouse embryonic stem cell (mESC) culture. Extensive research is conducted on reliable alternatives for LIF as its clinical application in stable culture and large‐scale expansion of ESCs is limited by its instability and high cost. However, few studies have sought to replace LIF with nanoparticles to provide a xeno‐free culture condition. MgAl‐LDH (layered double hydroxide) nanoparticles can partially replace LIF in maintaining pluripotency of mESCs; however, the requirement and tolerance for aluminum ions in mice are far lesser than those of iron ions. Hence, MgFe‐LDH nanoparticles are selected for this study. MgFe‐LDH is superior to MgAl‐LDH in maintaining self‐renewal and pluripotency of mESCs, in the absence of LIF and mouse embryonic fibroblast. Furthermore, combined transcriptomic and proteomic analysis confirms that MgFe‐LDH can activate the LIF receptor (LIFR)/phosphatidylinositol 3‐kinase (PI3K)/protein kinase B(AKT), LIFR/JAK/janus kinase (JAK)/signal transducer and activator of transcription 3(STAT3), and phospho‐signal transducer and activator of transcription 3(p‐STAT3)/ten‐eleven translocation (TET) signaling pathways, while the extra Fe²⁺ provided by MgFe‐LDH would also enhance TET1/2 abundance thus affecting the TET1/2 regulated pluripotency related marker expression and TET1/2 meditated DNA demethylation. These results suggest that MgFe‐LDH nanoparticles can thus be used as an affordable and efficient replacement for LIF in mESC cultivation.