Department of Pneumonology, University Hospital of Alexandroupolis, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
Respiration. 2013;85(3):179-92. doi: 10.1159/000346525. Epub 2013 Jan 29.
Chronic lung diseases such as idiopathic pulmonary fibrosis and cystic fibrosis or chronic obstructive pulmonary disease and asthma are leading causes of morbidity and mortality worldwide with a considerable human, societal and financial burden. In view of the current disappointing status of available pharmaceutical agents, there is an urgent need for alternative more effective therapeutic approaches that will not only help to relieve patient symptoms but will also affect the natural course of the respective disease. Regenerative medicine represents a promising option with several fruitful therapeutic applications in patients suffering from chronic lung diseases. Nevertheless, despite relative enthusiasm arising from experimental data, application of stem cell therapy in the clinical setting has been severely hampered by several safety concerns arising from the major lack of knowledge on the fate of exogenously administered stem cells within chronically injured lung as well as the mechanisms regulating the activation of resident progenitor cells. On the other hand, salient data arising from few 'brave' pilot investigations of the safety of stem cell treatment in chronic lung diseases seem promising. The main scope of this review article is to summarize the current state of knowledge regarding the application status of stem cell treatment in chronic lung diseases, address important safety and efficacy issues and present future challenges and perspectives. In this review, we argue in favor of large multicenter clinical trials setting realistic goals to assess treatment efficacy. We propose the use of biomarkers that reflect clinically inconspicuous alterations of the disease molecular phenotype before rigid conclusions can be safely drawn.
慢性肺部疾病,如特发性肺纤维化、囊性纤维化、慢性阻塞性肺疾病和哮喘,是全球发病率和死亡率的主要原因,给人类、社会和经济带来了巨大的负担。鉴于现有药物治疗的现状令人失望,迫切需要替代的更有效的治疗方法,这些方法不仅有助于缓解患者的症状,还能影响疾病的自然进程。再生医学是一种很有前途的选择,在慢性肺部疾病患者中有多种有希望的治疗应用。然而,尽管实验数据带来了一定的积极性,但由于对慢性损伤肺部中外源性给予的干细胞的命运以及调节驻留祖细胞激活的机制缺乏了解,干细胞治疗在临床环境中的应用受到了严重阻碍,干细胞疗法的应用仍受到多种安全问题的严重制约。另一方面,少数关于慢性肺部疾病中干细胞治疗安全性的“勇敢”试点研究的显著数据似乎很有前景。本文综述的主要目的是总结干细胞治疗在慢性肺部疾病中的应用现状,探讨重要的安全性和疗效问题,并提出未来的挑战和展望。在本文中,我们主张进行大型多中心临床试验,设定切合实际的目标来评估治疗效果。我们建议使用生物标志物来反映疾病分子表型在临床上不易察觉的变化,以便在得出可靠结论之前提供参考。