Table 2.
Published clinical trials of MSC therapy in COPD
| Registration code | Patients (n) | Design | Treatment | Year | Primary outcomes | Secondary outcomes | Safety results | Efficacy results |
|---|---|---|---|---|---|---|---|---|
| NCT0068372227 | Stage II/III COPD (n=62: 30 MSC; 32 placebo) | Multicenter, placebo-controlled, randomized, double-blind, Phase II safety and efficacy study | Allogeneic MSCs 1×108/mL, 4 IV doses (once a month) | April 2008 (2-year follow-up) | AEs occurrence: no serious or clinically relevant AEs and no significant changes in SaO2 or HR were observed during MSC infusion | Lung function: FEV1, FVC, FEV1/FVC, total capacity, DLCO, 6MWD, dyspnea (Borg scale) SGRQ, and global assessment Exacerbations: time to first exacerbation; exacerbation rate ratio between study arms Inflammation markers: TNF-α, IFN-γ, IL-2, TGF-β, IL-4, IL-5, IL-10, and CRP | AEs mostly mild to moderate (MSC 56.6%; placebo 65.6%) and unlikely to be procedure-related (MSC 63.3%; placebo 68.8%) | COPD exacerbations: MSC 66.7%; placebo 46.9% Mean time to first exacerbation: MSC 6.7 months versus placebo not estimated Exacerbation-free at 1- and 2-year follow-up: MSC 46.0% and 31.9%; placebo 56.3% and 52.7% |
| NCT0111025226 | Stage III/IV COPD, advanced emphysema (n=4) | Single center, single-arm, open-label safety study | Autologous BM-MCs 1×108/mL, single IV dose (brachial vein) | May 2009 (1 and 3-year follow-ups) | FVC, FEV1, and VC (days 0 and 30) | Arterial blood gases (days 0 and 30) | Safe, no significant AEs | Slightly improved lung function ≤30 days after infusion, declined thereafter, but not to baseline Three-year expiratory tests in two patients predicted FVC increase from 21%–36.5% to 34%–58%; all patients reported significantly improved emotional and physical status |
| NCT0130651345 | Stage III COPD, severe emphysema, eligible for LVRS (n=10) | Single arm, open-label safety study | Autologous BM-MSCs 1–2×106 cells/kg, 2 V doses (1 week apart, and 3 weeks before Second LVRS) | October 2010 (1-year follow-up) | Safety: AEs ≤3 weeks after infusion (WHO criteria) Feasibility: quantities of expanded MSCs in relation to the amount of BM collected; passages required and time to reach target dose | Difference (days) between post-LVRS transpleural air leak after first versus second LVRS; immuno-histochemistry for markers of inflammation, fibrosis, and repair in resected lung tissue | Safety: stable vital functions and no change in WHO-toxicity; no infusion-related symptoms Feasibility: 7/10 patients completed the study; BM could be aspirated from 9; target MSC number was obtained with 3 expansion cycles | Clinical: FEV1 increased by 390±240 mL from baseline at 1-year follow-up (p=0.03) Patients’ weight significantly increased: 4.6 kg (range 1–10 kg; p=0.016) Immuno-histochemistry: alveolar septa showed tripled expression of CD31 (p=0.016); CD3+ T cell count was significantly higher in alveolar septa after LVRS + BM-MSC versus baseline (p=0.016); CD4+ T cell count in alveolar septa increased in all but one patient after LVRS + BM-MSC (p=0.30; fold change p=0.047) Gene expression: higher mRNA expression of IL10 and TSG6 in biopsy tissue after versus before LVRS + BM-MSC (p=0.06) |
| NCT0187262446 | Stage III/IV COPD, severe heterogeneous emphysema (n=10: 5 EBV; 5 EBV + MSC) | Prospective, single-blind, randomized, placebo-controlled, Phase I safety study | Allogeneic BM-MSCs 108 cells/30 mL, instilled into each subsegmental airway division, immediately before EBV insertion into these same subsegments | December 2013 (30 and 90-day follow-up) | Absence of lung deficits during the procedure and at 4 month follow-up | Quality of Life (SGRQ), spirometry, flow-volume curve, post-bronchodilator test, determination of residual volume, airway resistance by plethysmography, DCLO, and 6MWD Inflammation (cytokines and CRP) | Safe, no patient in the EBV + MSC group experienced serious adverse events | 6MWD and BMI did not differ between EBV and EBV + MSCs groups At day 90, EBV + MSC patients had lower BODE index compared to baseline, and lower MMRC scores compared to baseline and day 30. Significant decreases in SGRQS, SGRQA, SGRQI, SGRQT scores were observed in the + MSCs group |
Abbreviations: 6MWD, 6-minute walk distance; AE, adverse events; BM, bone marrow; BMI, body mass index; BM-MC, bone marrow mononuclear cell; BM-MSC, bone marrow mesenchymal stromal cell; BODE index, Body-mass index, airflow Obstruction, Dyspnea, and Exercise; CRP, C-reactive protein; DLCO, diffusing capacity of carbon monoxide in lungs; EBV, endobronchial valve; FVC, forced vital capacity; FEV1, forced expiratory volume in 1 second; HR, heart rate; IFN-γ, interferon gamma; IL, interleukin; IV, intravenous; LVRS, lung volume reduction surgery; MMRC, modified medical research council dyspnea scale; SaO2, arterial oxygen saturation; SGRQS, St George’s Respiratory Questionnaire – Symptoms; SGRQA, St George’s Respiratory Questionnaire – Activity; SGRQI, St George’s Respiratory Questionnaire – Impacts; SGRQT, St George’s Respiratory Questionnaire – Total; TGF-β, transforming growth factor; TNF-α, tumor necrosis factor alpha; TSG6, tumor necrosis factor-inducible gene 6 protein; VC, vital capacity.