Lung injury and fibrosis represent the most significant outcomes of severe and acute lung disorders, including COVID-19. However, there are still no effective drugs to treat lung injury and fibrosis. In this study, we report the generation of clinical-grade human embryonic stem cells (hESCs)-derived immunity- and matrix-regulatory cells (IMRCs) produced under good manufacturing practice requirements, that can treat lung injury and fibrosis in vivo. We generate IMRCs by sequentially differentiating hESCs with serum-free reagents. IMRCs possess a unique gene expression profile distinct from that of umbilical cord mesenchymal stem cells (UCMSCs), such as higher expression levels of proliferative, immunomodulatory and anti-fibrotic genes. Moreover, intravenous delivery of IMRCs inhibits both pulmonary inflammation and fibrosis in mouse models of lung injury, and significantly improves the survival rate of the recipient mice in a dose-dependent manner, likely through paracrine regulatory mechanisms. IMRCs are superior to both primary UCMSCs and the FDA-approved drug pirfenidone, with an excellent efficacy and safety profile in mice and monkeys. In light of public health crises involving pneumonia, acute lung injury and acute respiratory distress syndrome, our findings suggest that IMRCs are ready for clinical trials on lung disorders.

肺损伤和纤维化代表了包括 COVID-19 在内的严重和急性肺部疾病的最重要结果。然而，仍然没有有效的药物来治疗肺损伤和纤维化。在这项研究中，我们报告了根据良好生产规范要求生产的临床级人类胚胎干细胞 (hESCs) 衍生的免疫和基质调节细胞 (IMRCs)，可在体内治疗肺损伤和纤维化。我们通过用无血清试剂顺序区分 hESCs 来生成 IMRCs。IMRCs 具有与脐带间充质干细胞 (UCMSCs) 不同的独特基因表达谱，例如增殖、免疫调节和抗纤维化基因的更高表达水平。而且，IMRCs 的静脉给药可抑制肺损伤小鼠模型中的肺部炎症和纤维化，并以剂量​​依赖性方式显着提高受体小鼠的存活率，可能是通过旁分泌调节机制。IMRCs 优于原发性 UCMSCs 和 FDA 批准的药物吡非尼酮，在小鼠和猴子中具有出色的疗效和安全性。鉴于涉及肺炎、急性肺损伤和急性呼吸窘迫综合征的公共卫生危机，我们的研究结果表明 IMRC 已准备好进行肺部疾病的临床试验。在小鼠和猴子中具有出色的疗效和安全性。鉴于涉及肺炎、急性肺损伤和急性呼吸窘迫综合征的公共卫生危机，我们的研究结果表明 IMRC 已准备好进行肺部疾病的临床试验。在小鼠和猴子中具有出色的疗效和安全性。鉴于涉及肺炎、急性肺损伤和急性呼吸窘迫综合征的公共卫生危机，我们的研究结果表明 IMRC 已准备好进行肺部疾病的临床试验。