Paean Biotechnology, Inc. 5 Samil-daero8-gil, Jung-gu, Seoul, 04552, Korea.
Jeonbuk Branch Institute, Korea Institute of Toxicology, Jeongeup, 56212, Korea.
BMC Pulm Med. 2024 Sep 27;24(1):477. doi: 10.1186/s12890-024-03304-2.
The mitochondria are essential organelles not only providing cellular energy in the form of ATP, but also regulating the inflammatory response and the cell death program. Mitochondrial dysfunction has been associated with various human diseases, including metabolic syndromes as well as inflammatory and neurodegenerative diseases. Acute respiratory distress syndrome (ARDS) is an acute pulmonary disorder characterized by uncontrolled alveolar inflammation, apoptotic lung epithelial/endothelial cells, and pulmonary edema. Despite the high mortality of ARDS, an effective pharmacotherapy to treat this disease has not been established yet. Therefore, identifying a novel targeted therapy for ARDS is important. Recently, exogenous mitochondrial transplantation was reported to be beneficial for treating mitochondrial dysfunction. The current study aimed to investigate the therapeutic effect of mitochondrial transplantation on ARDS in vitro and in vivo.
Mitochondria were isolated from human stem cells. For in vitro efficacy of mitochondrial transplantation on the inflammation and cell death, murine alveolar macrophages MH-S and human pulmonary microvascular endothelial cells HPMECs were exposed to LPS, respectively. The ARDS mice model established by a single intratracheal instillation of LPS was used for in vivo efficacy of intravenously treated mitochondria.
Our results showed that the mitochondria isolated from human stem cells exhibited an anti-inflammatory effect against alveolar macrophages and an anti-apoptotic effect against the alveolar epithelial cells. Furthermore, intravenous mitochondrial treatment was associated with the attenuation of lung injury in the LPS-induced ARDS mice.
Dual effects of mitochondria on anti-inflammation and anti-apoptosis support the potential of mitochondrial transplantation as a novel therapeutic strategy for ARDS.
线粒体不仅提供细胞能量（形式为 ATP），还是调节炎症反应和细胞死亡程序的必需细胞器。线粒体功能障碍与各种人类疾病有关，包括代谢综合征以及炎症和神经退行性疾病。急性呼吸窘迫综合征（ARDS）是一种以肺泡炎症失控、肺泡上皮/内皮细胞凋亡和肺水肿为特征的急性肺部疾病。尽管 ARDS 的死亡率很高，但尚未建立有效的药物治疗方法。因此，确定治疗 ARDS 的新靶向疗法很重要。最近，有报道称外源性线粒体移植对治疗线粒体功能障碍有益。本研究旨在体外和体内研究线粒体移植对 ARDS 的治疗效果。
从人干细胞中分离出线粒体。对于线粒体移植对炎症和细胞死亡的体外疗效，分别用 LPS 处理鼠肺泡巨噬细胞 MH-S 和人肺微血管内皮细胞 HPMEC。通过单次气管内滴注 LPS 建立 ARDS 小鼠模型，用于静脉注射线粒体的体内疗效。
我们的结果表明，从人干细胞中分离出的线粒体对肺泡巨噬细胞具有抗炎作用，对肺泡上皮细胞具有抗凋亡作用。此外，静脉注射线粒体治疗与 LPS 诱导的 ARDS 小鼠肺损伤的减轻有关。
线粒体对抗炎和抗凋亡的双重作用支持线粒体移植作为 ARDS 新治疗策略的潜力。
