Induced pluripotent stem cell–derived neural progenitor cells coculturing promotes mice cortical astrocytes antiapoptosis via nuclear factor erythroid 2-related factor 2/heme oxygenase-1 axis in vitro

Background Intracerebral hemorrhage (ICH) induces secondary brain injury, driven in part by oxidative stress caused by hemin, a toxic hemoglobin breakdown product. Cortical astrocytes, critical for maintaining redox homeostasis, are vulnerable to hemin-induced oxidative damage, exacerbating neuronal injury. Induced pluripotent stem cell–derived neural progenitor cells (iPSC-NPCs) have shown therapeutic potential in brain injury models by promoting neural repair, but their ability to protect astrocytes against hemin toxicity remains unexplored. We hypothesized that iPSC-NPCs coculture mitigates hemin-induced oxidative stress in astrocytes by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) antioxidant pathway. Materials and methods Astrocytes were exposed to hemin with or without iPSC-NPC coculture. We assessed cell viability, reactive oxygen species (ROS) accumulation, apoptosis, and the role of the Nrf2/HO-1 pathway using small-interfering RNA. Results iPSC-NPC coculture significantly reduced hemin-induced oxidative damage by promoting Nrf2 nuclear translocation and upregulating HO-1, thereby decreasing ROS and apoptosis. Silencing Nrf2 abolished these protective effects. Conclusion Our findings demonstrate that iPSC-NPCs protect astrocytes from hemin toxicity via the Nrf2/HO-1 pathway, suggesting a novel therapeutic strategy for ICH-induced oxidative injury.