Clinical application of stem/stromal cells in COPD

Abstract

Chronic obstructive pulmonary disease (COPD) is a progressive life-threatening disease that is significantly increasing in prevalence and is predicted to become the third leading cause of death worldwide by 2030. At present, there are no true curative treatments that can stop the progression of the disease, and new therapeutic strategies are desperately needed. Advances in cell-based therapies provide a platform for the development of new therapeutic approaches in severe lung diseases such as COPD. At present, a lot of focus is on mesenchymal stem (stromal) cell (MSC)-based therapies, mainly due to their immunomodulatory properties. Despite increasing number of preclinical studies demonstrating that systemic MSC administration can prevent or treat experimental COPD and emphysema, clinical studies have not been able to reproduce the preclinical results and to date no efficacy or significantly improved lung function or quality of life has been observed in COPD patients. Importantly, the completed appropriately conducted clinical trials uniformly demonstrate that MSC treatment in COPD patients is well tolerated and no toxicities have been observed. All clinical trials performed so far, have been phase I/II studies, underpowered for the detection of potential efficacy. There are several challenges ahead for this field such as standardized isolation and culture procedures to obtain a cell product with high quality and reproducibility, administration strategies, improvement of methods to measure outcomes, and development of potency assays. Moreover, COPD is a complex pathology with a diverse spectrum of clinical phenotypes, and therefore it is essential to develop methods to select the subpopulation of patients that is most likely to potentially respond to MSC administration. In this chapter, we will discuss the current state of the art of MSC-based cell therapy for COPD and the hurdles that need to be overcome.