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

Plain Language Summary 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. Plain Language Summary Intracerebral hemorrhage (ICH) can cause brain damage due to oxidative stress from hemin, a toxic breakdown product of hemoglobin. This study explored whether induced pluripotent stem cell-derived neural progenitor cells (iPSC-NPCs) can protect astrocytes, which are crucial for brain health, from hemin-induced damage. Researchers found that when astrocytes were cocultured with iPSC-NPCs, oxidative stress and cell death were reduced. This protective effect was linked to the activation of the Nrf2/HO-1 antioxidant pathway. Silencing Nrf2 negated the benefits, highlighting the pathway's importance. These findings suggest iPSC-NPCs could be a promising treatment for oxidative injury in ICH. Text is machine generated and may contain inaccuracies. FAQ