Human placenta–derived stem cells (hPSCs) with the therapeutic potential to recover from optic nerve injury have been reported. We have recently demonstrated that hPSCs have protective abilities against hypoxic damage. To improve the capacity of hPSCs, we established a hypoxia-preconditioned strain (HPPCs) using a hypoxic chamber. The hPSCs were exposed to short-term hypoxic conditions of 2.2% O₂ and 5.5% CO₂. We also performed in vivo experiments to demonstrate the recovery effects of HPPCs using an optic nerve injury rat model. Naïve hPSCs (and HPPCs) were injected into the optic nerve. After 1, 2, or 4 weeks, we analyzed changes in target proteins in the optic nerve tissues. In the retina, GAP43 expression was higher in both groups of naïve hPSCs and HPPCs versus sham controls. Two weeks after injection, all hPSC-injected groups showed recovery of tuj1 expression in damaged retinas. We also determined GFAP expression in retinas using the same model. In optic nerve tissues, HIF-1α levels were significantly lower in the HPPC-injected group 1 week after injury, and Thy-1 levels were higher in the hPSC-injected group at 4 weeks. There was also an enhanced recovery of Thy-1 expression after HPPC injection. In addition, R28 cells exposed to hypoxic conditions showed improved viability through enhanced recovery of HPPCs than naïve hPSCs. VEGF protein was a mediator in the recovery pathway via upregulation of target proteins regulated by HPPCs. Our results suggest that HPPCs may be candidates for cell therapy for the treatment of traumatic optic nerve injury.

已经报道了具有从视神经损伤中恢复的治疗潜力的人胎盘衍生干细胞 (hPSC)。我们最近证明 hPSCs 具有抵抗缺氧损伤的保护能力。为了提高 hPSC 的能力，我们使用缺氧室建立了缺氧预处理菌株 (HPPC)。_{hPSCs 暴露于 2.2% O 2}和 5.5% CO ₂的短期缺氧条件下. 我们还使用视神经损伤大鼠模型进行了体内实验，以证明 HPPC 的恢复效果。将幼稚的 hPSC（和 HPPC）注射到视神经中。1、2 或 4 周后，我们分析了视神经组织中靶蛋白的变化。在视网膜中，与假对照组相比，两组幼稚 hPSC 和 HPPC 的 GAP43 表达均较高。注射后两周，所有注射 hPSC 的组均显示受损视网膜中 tuj1 表达的恢复。我们还使用相同的模型确定了视网膜中的 GFAP 表达。在视神经组织中，HPPC 注射组损伤后 1 周 HIF-1α 水平显着降低，而 hPSC 注射组损伤 4 周 Thy-1 水平升高。HPPC 注射后 Thy-1 表达的恢复也有所提高。此外，与初始 hPSC 相比，暴露于缺氧条件下的 R28 细胞通过增强 HPPC 的回收率显示出更高的活力。VEGF 蛋白是通过 HPPC 调节的靶蛋白上调恢复途径中的介质。我们的研究结果表明，HPPC 可能是用于治疗外伤性视神经损伤的细胞疗法的候选者。