Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Adv Exp Med Biol. 2018;1103:293-303. doi: 10.1007/978-4-431-56847-6_16.
Ischemia-reperfusion injury (IRI) is one of the main causes of primary graft dysfunction that accounts for 25% of mortality after lung transplantation. Disruption of blood supply and subsequent reperfusion result in organ damage with activating innate and adaptive immune response, leading to inflammatory insults. The IRI after lung transplantation is primarily manifested by permeability pulmonary edema on the basis of pulmonary vascular endothelial cell injury as seen in acute respiratory distress syndrome (ARDS). Stem cells have potent anti-inflammatory and immunomodulatory properties through local paracrine mechanisms. The application of mesenchymal stem cells (MSCs) for ARDS as well as IRI in various organs, therefore, has been interested and extensively investigated in animal models with promising results. Furthermore, two recent clinical randomized, placebo-controlled pilot studies demonstrated that treatment of ARDS with MSCs appears to be safe and feasible.Muse cells are stress-tolerant and non-tumorigenic endogenous pluripotent-like stem cells. They comprise small proportions of cultured fibroblasts and MSCs and can be isolated from these populations. Muse cells are known to migrate to the damaged tissue after local or systemic administration, spontaneously differentiate into the tissue-compatible cells, and also secrete factors related to immunomodulation and tissue repair. We have recently shown the effect of Muse cells on ameliorating lung IRI in a rat model. With 2 h of warm ischemia and subsequent reperfusion on the left lung, the lung showed severe pulmonary edema. Administration of Muse cell through the left pulmonary artery immediately after reperfusion more significantly improved lung oxygenation capacity, compliance, and histological damage on days 1 and 3 after reperfusion compared with MSCs, and this was associated with higher expression levels of proteins related with anti-inflammation and tissue repair in the lung. Encouraging results of this study advocate further investigation of the ability of Muse cells to prevent and treat IRI after lung transplantation.
缺血再灌注损伤（IRI）是原发性移植物功能障碍的主要原因之一，占肺移植后死亡率的 25%。血液供应中断和随后的再灌注导致器官损伤，激活固有和适应性免疫反应，导致炎症损伤。肺移植后的 IRI 主要表现为肺血管内皮细胞损伤基础上的通透性肺水肿，类似于急性呼吸窘迫综合征（ARDS）。干细胞通过局部旁分泌机制具有强大的抗炎和免疫调节特性。因此，间充质干细胞（MSCs）在 ARDS 以及各种器官的 IRI 中的应用已在动物模型中受到关注并进行了广泛研究，结果有一定前景。此外，最近两项临床随机、安慰剂对照的初步研究表明，MSCs 治疗 ARDS 似乎是安全可行的。Muse 细胞是具有应激耐受性和非致瘤性的内源性多能样干细胞。它们占培养成纤维细胞和 MSCs 的小比例，可以从这些细胞群中分离出来。已知 Muse 细胞在局部或全身给药后会迁移到受损组织，自发分化为组织相容的细胞，并分泌与免疫调节和组织修复相关的因子。我们最近研究了 Muse 细胞对改善大鼠肺 IRI 的影响。在左肺 2 小时热缺血和随后的再灌注后，肺部出现严重的肺水肿。与 MSCs 相比，在再灌注后立即通过左肺动脉给予 Muse 细胞治疗，在再灌注后第 1 天和第 3 天，显著改善了肺氧合能力、顺应性和组织学损伤，并且与肺中与抗炎和组织修复相关的蛋白表达水平升高相关。这项研究的令人鼓舞的结果提倡进一步研究 Muse 细胞预防和治疗肺移植后 IRI 的能力。
