Antunes Mariana A, Lapa E Silva José Roberto, Rocco Patricia Rm
Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro (UFRJ), RJ, Brazil.
National Institute of Science and Technology for Regenerative Medicine, Rio de Janeiro, RJ, Brazil.
Int J Chron Obstruct Pulmon Dis. 2017 Oct 16;12:3017-3027. doi: 10.2147/COPD.S146671. eCollection 2017.
COPD is the most frequent chronic respiratory disease and a leading cause of morbidity and mortality. The major risk factor for COPD development is cigarette smoke, and the most efficient treatment for COPD is smoking cessation. However, even after smoking cessation, inflammation, apoptosis, and oxidative stress may persist and continue contributing to disease progression. Although current therapies for COPD (primarily based on anti-inflammatory agents) contribute to the reduction of airway obstruction and minimize COPD exacerbations, none can avoid disease progression or reduce mortality. Within this context, recent advances in mesenchymal stromal cell (MSC) therapy have made this approach a strong candidate for clinical use in the treatment of several pulmonary diseases. MSCs can be readily harvested from diverse tissues and expanded with high efficiency, and have strong immunosuppressive properties. Preclinical studies have demonstrated encouraging outcomes of MSCs therapy for lung disorders, including emphysema. These findings instigated research groups to assess the impact of MSCs in human COPD/emphysema, but clinical results have fallen short of expectations. However, MSCs have demonstrated a good adjuvant role in the clinical scenario. Trials that used MSCs combined with another, primary treatment (eg, endobronchial valves) found that patients derived greater benefit in pulmonary function tests and/or quality of life reports, as well as reductions in systemic markers of inflammation. The present review summarizes and describes the more recent preclinical studies that have been published about MSC therapy for COPD/emphysema and discusses what has already been applied about MSCs treatment in COPD patients in the clinical setting.
慢性阻塞性肺疾病(COPD)是最常见的慢性呼吸道疾病,也是发病和死亡的主要原因。COPD发生的主要危险因素是香烟烟雾,而COPD最有效的治疗方法是戒烟。然而,即使戒烟后,炎症、细胞凋亡和氧化应激仍可能持续存在,并继续促使疾病进展。尽管目前用于COPD的治疗方法(主要基于抗炎药物)有助于减轻气道阻塞并尽量减少COPD急性加重,但没有一种方法能够避免疾病进展或降低死亡率。在此背景下,间充质基质细胞(MSC)治疗的最新进展使这种方法成为治疗多种肺部疾病的有力临床应用候选方法。MSC可以很容易地从不同组织中获取并高效扩增,并且具有强大的免疫抑制特性。临床前研究已证明MSC治疗肺部疾病(包括肺气肿)的结果令人鼓舞。这些发现促使研究小组评估MSC对人类COPD/肺气肿的影响,但临床结果未达预期。然而,MSC在临床情况下已显示出良好的辅助作用。使用MSC与另一种主要治疗方法(如支气管内瓣膜)联合的试验发现,患者在肺功能测试和/或生活质量报告中获益更大,全身炎症标志物也有所降低。本综述总结并描述了最近发表的关于MSC治疗COPD/肺气肿的临床前研究,并讨论了在临床环境中已应用于COPD患者的MSC治疗情况。