Optimized Mesenchymal Stem Cell Therapy for Chronic Obstructive Pulmonary Disease

PurposeBackground: Chronic obstructive pulmonary disease is both an obstructive and inflammatory disease. Mesenchymal stem cell (MSC) therapy has shown early promise to modulate inflammation and improve lung function. The therapy has limitations resulting from cell loss and sub-optimal delivery. Our goal was to develop a MSC therapy that can use the inflammation in the lungs which results in SDF-1 expression as a target.MethodsPatients with severe COPD were randomized to receive either saline, MSCs, or MSCs primed with CXCR4 protein (the natural ligand for SDF-1). All clinical events along with pulmonary functions tests (FEV1/FVC) and oxygen requirements were evaluated.ResultsThirty patients successfully were enrolled in the study. All patients were prior or recent smokers. There were no acute adverse events. The MSC and MSC+CXCR4 group demonstrated improvement in pulmonary functions tests and oxygen requirement compared to the control group.ConclusionTargeted MSC therapy with CXCR4 demonstrates safety along with promising results in patients with chronic pulmonary obstruction disease. Larger trials and follow up will be required to evaluate benefit and sustainability.Tabled 1Pulmonary OutcomesGroupPlacebon=5pIVn=5pInhaledn=5Bothn=5pBothn=5FEV1/FVC pre0.53±0.160.49±0.080.51±0.040.47±0.070.48±0.05FEV1/FVC post0.49±0.150.58±0.200.57±0.110.62±0.050.71±0.08O2L/min pre3.1±1.22.9±1.63.1±1.12.8±1.22.8±1.2O2L/min post3.2±1.51.7±1.62.0±1.32.1±1.11.5±1.2MAP/CE20000 Open table in a new tab PurposeBackground: Chronic obstructive pulmonary disease is both an obstructive and inflammatory disease. Mesenchymal stem cell (MSC) therapy has shown early promise to modulate inflammation and improve lung function. The therapy has limitations resulting from cell loss and sub-optimal delivery. Our goal was to develop a MSC therapy that can use the inflammation in the lungs which results in SDF-1 expression as a target. Background: Chronic obstructive pulmonary disease is both an obstructive and inflammatory disease. Mesenchymal stem cell (MSC) therapy has shown early promise to modulate inflammation and improve lung function. The therapy has limitations resulting from cell loss and sub-optimal delivery. Our goal was to develop a MSC therapy that can use the inflammation in the lungs which results in SDF-1 expression as a target. MethodsPatients with severe COPD were randomized to receive either saline, MSCs, or MSCs primed with CXCR4 protein (the natural ligand for SDF-1). All clinical events along with pulmonary functions tests (FEV1/FVC) and oxygen requirements were evaluated. Patients with severe COPD were randomized to receive either saline, MSCs, or MSCs primed with CXCR4 protein (the natural ligand for SDF-1). All clinical events along with pulmonary functions tests (FEV1/FVC) and oxygen requirements were evaluated. ResultsThirty patients successfully were enrolled in the study. All patients were prior or recent smokers. There were no acute adverse events. The MSC and MSC+CXCR4 group demonstrated improvement in pulmonary functions tests and oxygen requirement compared to the control group. Thirty patients successfully were enrolled in the study. All patients were prior or recent smokers. There were no acute adverse events. The MSC and MSC+CXCR4 group demonstrated improvement in pulmonary functions tests and oxygen requirement compared to the control group. ConclusionTargeted MSC therapy with CXCR4 demonstrates safety along with promising results in patients with chronic pulmonary obstruction disease. Larger trials and follow up will be required to evaluate benefit and sustainability.Tabled 1Pulmonary OutcomesGroupPlacebon=5pIVn=5pInhaledn=5Bothn=5pBothn=5FEV1/FVC pre0.53±0.160.49±0.080.51±0.040.47±0.070.48±0.05FEV1/FVC post0.49±0.150.58±0.200.57±0.110.62±0.050.71±0.08O2L/min pre3.1±1.22.9±1.63.1±1.12.8±1.22.8±1.2O2L/min post3.2±1.51.7±1.62.0±1.32.1±1.11.5±1.2MAP/CE20000 Open table in a new tab Targeted MSC therapy with CXCR4 demonstrates safety along with promising results in patients with chronic pulmonary obstruction disease. Larger trials and follow up will be required to evaluate benefit and sustainability.