Mesenchymal stromal cell therapy in COPD: from bench to bedside

Abstract

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.

The Potential of Mesenchymal Stem Cells to Treat Systemic Inflammation in Horses

“…In humans, it is reported that MSCs act independent of the route of administration (intravenous v. intratracheal). Immunomodulatory effects are more predominant with intravenous injection compared to reparative mechanism being predominant with intratracheal administration (86). An in vitro study looking at the response of LPS-stimulated equine alveolar macrophages after exposure to conditioned medium and microvesicles from amniotic MSCs showed there was a significant decrease in TNF-α production in the groups treated with the MSC derivatives when compared to controls (87).…”

Clinical Application of Mesenchymal Stem Cell-Derived Extracellular Vesicle-Based Therapeutics for Inflammatory Lung Diseases

“…Furthermore, MSCs have been shown to possess anti-inflammatory and anti-fibrotic properties due to the secretion of various cytokines and soluble factors, which affects various immune cells and promotes tissue generation [ 38 ]. MSCs can interact with alveolar macrophages via cell-to-cell contact and promote their reprogramming via the cyclooxygenase-2 (COX2)-mediated prostaglandin E2 production [ 39 , 40 ]. According to the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy established in 2006, the minimal identifying characteristics for human MSCs are [ 41 ]: (i) an MSC must be plastic-adherent when maintained in standard culture conditions; (ii) an MSC must express CD105, CD73 and CD90 and lack expression of CD45, CD34, CD14 or CD11b, CD79a or CD19 and HLA-DR surface molecules; and (iii) an MSC must be able to differentiate into osteoblasts, adipocytes and chondrocytes in vitro.…”

Molecular and Cellular Mechanisms Responsible for Beneficial Effects of Mesenchymal Stem Cell-Derived Product “Exo-d-MAPPS” in Attenuation of Chronic Airway Inflammation

“…MSCs are self-renewable, multipotent cells which are able to differentiate into alveolar epithelial cells and are able to modulate the proliferation, activation, and effector function of all immune cells that play an important role in the development, progression, and exacerbation of COPD [14]. Accordingly, several experimental studies demonstrated the beneficial effects of MSCs in the treatment of COPD [15][16][17][18].…”