Authors: Henry E. Young, Mark O. Speight
The major risk factor for chronic obstructive pulmonary disease (COPD) is cigarette smoking which drives an inflammatory process that causes loss of function. Cessation of smoking, oxygen therapy, various inhalers, medications to improve vasodilation, antibiotics to combat the frequent lung infections, fluid replacement, exercise rehabilitation programs, and early detection and treatment of comorbidities are the options available to patients with COPD to reduce the burden of the disease, but do not alter the underlying progression of COPD. Lung transplantation is an increasingly discussed therapeutic option, but its use remains limited. The median survival time after lung transplant is 4.5 years. Currently, regenerative therapies are divided into extrinsic (stem cells) and intrinsic (small molecules) therapeutic strategies. The immunomodulatory effects of mesenchymal stem cells were tested in clinical trials. Systemic infusion was safe in moderate to severe COPD, but no improvement in lung function was noted. Infusion of small molecules failed in preliminary clinical trials, possibly due to the severity of the COPD. In culture, telomerase-positive stem cells were shown to differentiate into cells of the lung and in
a pre-clinical animal model of lung fibrosis infusion of these same stem cells demonstrated a regeneration of bronchioles, alveolar ducts, and alveolar sacs. We hypothesized that telomerase-positive stem cells would increase lung function in individuals with COPD. In a phase-I safety study, individuals (n=51) with very severe (GOLD4) and severe (GOLD-3) COPD were treated with autologous and/or allogeneic telomerase-positive stem cells. Results from an eight-year follow-up study demonstrated an increase in their FEV1 ’s from 0% to 16% above pretreatment baseline values, with no adverse side effects. These results suggest that telomerase-positive stem cells are both safe and efficacious for the treatment of COPD.