Enhancing spinal cord injury repair through PTCH1-mediated neural progenitor cell differentiation induced by ion...

Spinal cord injury (SCI) is associated with profound neurological impairments, and to date, efficacious therapeutic interventions remain elusive. Embryonic stem cells (ESCs) possess the totipotent capacity to differentiate into specific neuronal cell types under the influence of appropriate extrinsic signals. Notably, their induction into neural progenitor cells (NPCs) holds particular promise. These NPCs are capable of self-renewal and can differentiate into all neuronal cell types, exhibiting the ability to migrate and integrate into damaged areas of the central nervous system (CNS), thereby emerging as an ideal therapeutic strategy for neurological disorders. Layered double hydroxides (LDHs), with their lamellar architecture, are biocompatible and possess anion-exchange attributes, making them prominent in drug and nucleotide delivery for tissue engineering. Nevertheless, the investigation into the intrinsic biological effects of LDHs are rarely reported. Our research demonstrates that MgFe-LDH and MgAl-LDH promote NPCs differentiation in a dose-dependent manner, and MgAl-LDH is superior to MgFe-LDH in promoting NPCs differentiation. RNAseq revealed that the promoted NPCs differentiation by nanoparticles was primarily associated with the interaction between nanoparticles and transmembrane protein PTCH1. Furthermore, we performed PTCH1 knockdown in NPCs and observed a significant impact on the MgAl-LDH-induced NPCs differentiation. In vivo, MgAl-LDH-pretreated NPCs implantation significantly enhances the behavioral and electrophysiological performance of SCI mice, and neurons clearly observed in the lesion sites of MgAl-LDH-pretreated NPCs group. This work provides novel strategies and a theoretical foundation for the research on nanomaterial regulation of stem cells fate and neural regenerative repair.